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2. Molecular and translational advances in meningiomas

Author

Suppiah S., Nassiri F., Bi W. L., Dunn I. F., Hanemann C. O., Horbinski C. M., Hashizume R., James C. D., Mawrin C., Noushmehr H., Perry A., Sahm F., Sloan A., Von Deimling A., Wen P. Y., Aldape K., Zadeh G., Au K., Barnhartz-Sloan J., Brastianos P. K., Butowski N., Carlotti C., Cusimano M. D., Dimeco F., Drummond K., Galanis E., Giannini C., Goldbrunner R., Griffith B., Herold-Mende C., Huang R. Y., James D., Jenkinson M. D., Jungk C., Kaufman T. J., Krischek B., Lachance D., Lafougere C., Lee I., Liu J. C., Mamatjan Y., Mansouri A., McDermott M., Munoz D., Ng H. -K., Pirouzmand F., Poisson L. M., Pollo B., Raleigh D., Saladino A., Santarius T., Schichor C., Schultz D., Schmidt N. O., Selman W., Spears J., Snyder J., Tabatabai G., Tatagiba M., Tirapelli D., Tonn J. C., Tsang D., Vogelbaum M. A., Deimling A. V., Walbert T., Westphal M., Workewych A. M., Suppiah S., Nassiri F., Bi W.L., Dunn I.F., Hanemann C.O., Horbinski C.M., Hashizume R., James C.D., Mawrin C., Noushmehr H., Perry A., Sahm F., Sloan A., Von Deimling A., Wen P.Y., Aldape K., Zadeh G., Au K., Barnhartz-Sloan J., Brastianos P.K., Butowski N., Carlotti C., Cusimano M.D., Dimeco F., Drummond K., Galanis E., Giannini C., Goldbrunner R., Griffith B., Herold-Mende C., Huang R.Y., James D., Jenkinson M.D., Jungk C., Kaufman T.J., Krischek B., Lachance D., Lafougere C., Lee I., Liu J.C., Mamatjan Y., Mansouri A., McDermott M., Munoz D., Ng H.-K., Pirouzmand F., Poisson L.M., Pollo B., Raleigh D., Saladino A., Santarius T., Schichor C., Schultz D., Schmidt N.O., Selman W., Spears J., Snyder J., Tabatabai G., Tatagiba M., Tirapelli D., Tonn J.C., Tsang D., Vogelbaum M.A., Deimling A.V., Walbert T., Westphal M., and Workewych A.M.

Subjects
Cancer Research, Supplement Articles, Genomics, Intracranial Neoplasm, sporadic meningioma, Bioinformatics, World health, Translational Research, Biomedical, Meningioma, 03 medical and health sciences, biomolecular, 0302 clinical medicine, Meningeal Neoplasms, otorhinolaryngologic diseases, medicine, Recurrent disease, Humans, Meningeal Neoplasm, Molecular Targeted Therapy, xenograft, Stage (cooking), neoplasms, MENINGIOMA, business.industry, cell line, Prognosis, medicine.disease, Combined Modality Therapy, nervous system diseases, 3. Good health, Clinical trial, Oncology, 030220 oncology & carcinogenesis, Neurology (clinical), genetic, business, epigenetic, 030217 neurology & neurosurgery
Abstract

Meningiomas are the most common primary intracranial neoplasm. The current World Health Organization (WHO) classification categorizes meningiomas based on histopathological features, but emerging molecular data demonstrate the importance of genomic and epigenomic factors in the clinical behavior of these tumors. Treatment options for symptomatic meningiomas are limited to surgical resection where possible and adjuvant radiation therapy for tumors with concerning histopathological features or recurrent disease. At present, alternative adjuvant treatment options are not available in part due to limited historical biological analysis and clinical trial investigation on meningiomas. With advances in molecular and genomic techniques in the last decade, we have witnessed a surge of interest in understanding the genomic and epigenomic landscape of meningiomas. The field is now at the stage to adopt this molecular knowledge to refine meningioma classification and introduce molecular algorithms that can guide prediction and therapeutics for this tumor type. Animal models that recapitulate meningiomas faithfully are in critical need to test new therapeutics to facilitate rapid-cycle translation to clinical trials. Here we review the most up-to-date knowledge of molecular alterations that provide insight into meningioma behavior and are ready for application to clinical trial investigation, and highlight the landscape of available preclinical models in meningiomas.

Published
2019
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3. Life after surgical resection of a meningioma: a prospective cross-sectional study evaluating health-related quality of life

Author

Nassiri F., Price B., Shehab A., Au K., Cusimano M. D., Jenkinson M. D., Jungk C., Mansouri A., Santarius T., Suppiah S., Teng K. X., Toor G. S., Zadeh G., Walbert T., Drummond K. J., Aldape K., Barnhartz-Sloan J., Bi W. L., Brastianos P. K., Butowski N., Carlotti C., Dimeco F., Dunn I. F., Galanis E., Giannini C., Goldbrunner R., Griffith B., Hashizume R., Hanemann C. O., Herold-Mende C., Horbinski C., Huang R. Y., James D., Kaufman T. J., Krischek B., Lachance D., Lafougere C., Lee I., Liu J. C., Mamatjan Y., Mawrin C., McDermott M., Munoz D., Noushmehr H., Ng H. -K., Perry A., Pirouzmand F., Poisson L. M., Pollo B., Raleigh D., Sahm F., Saladino A., Schichor C., Schultz D., Schmidt N. O., Selman W., Sloan A., Spears J., Snyder J., Tabatabai G., Tatagiba M., Tirapelli D., Tonn J. C., Tsang D., Vogelbaum M. A., Deimling A. V., Wen P. Y., Westphal M., Workewych A. M., Nassiri F., Price B., Shehab A., Au K., Cusimano M.D., Jenkinson M.D., Jungk C., Mansouri A., Santarius T., Suppiah S., Teng K.X., Toor G.S., Zadeh G., Walbert T., Drummond K.J., Aldape K., Barnhartz-Sloan J., Bi W.L., Brastianos P.K., Butowski N., Carlotti C., Dimeco F., Dunn I.F., Galanis E., Giannini C., Goldbrunner R., Griffith B., Hashizume R., Hanemann C.O., Herold-Mende C., Horbinski C., Huang R.Y., James D., Kaufman T.J., Krischek B., Lachance D., Lafougere C., Lee I., Liu J.C., Mamatjan Y., Mawrin C., McDermott M., Munoz D., Noushmehr H., Ng H.-K., Perry A., Pirouzmand F., Poisson L.M., Pollo B., Raleigh D., Sahm F., Saladino A., Schichor C., Schultz D., Schmidt N.O., Selman W., Sloan A., Spears J., Snyder J., Tabatabai G., Tatagiba M., Tirapelli D., Tonn J.C., Tsang D., Vogelbaum M.A., Deimling A.V., Wen P.Y., Westphal M., and Workewych A.M.

Subjects
Male, cognition, Cancer Research, medicine.medical_specialty, Cross-sectional study, insomnia, Population, Neurosurgery, Supplement Articles, meningioma, surgery, Meningioma, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Surveys and Questionnaires, Internal medicine, Meningeal Neoplasms, otorhinolaryngologic diseases, medicine, Humans, Longitudinal Studies, Prospective Studies, Prospective cohort study, education, education.field_of_study, business.industry, COGNIÇÃO, Cognition, Middle Aged, Prognosis, medicine.disease, humanities, 3. Good health, health-related quality of life, Cross-Sectional Studies, Oncology, 030220 oncology & carcinogenesis, Quality of Life, Female, fatigue, Neurology (clinical), business, 030217 neurology & neurosurgery, Follow-Up Studies, Cohort study
Abstract

Background Few studies have evaluated the health-related quality of life (HRQoL) of patients with meningiomas. Here, we report the largest prospective, longitudinal cross-sectional cohort study of HRQoL in meningiomas to date, in order to identify possible actionable determinants of global HRQoL. Methods Adults who had undergone resection of a grade I intracranial meningioma and were in routine follow-up at a single large tertiary center underwent HRQoL assessment using the QLQ-C30 questionnaire administered opportunistically at follow-up visits. Averaged transformed QLQ-C30 scores at 12-month intervals were compared with scores from a normative reference population, with reference to known minimal clinically meaningful difference (CMD) in scores. To evaluate for possible determinants of changes in global HRQoL, global HRQoL scores were correlated (Spearman's Rho) with subdomain and symptom scores and with interval time from surgical resection. Results A total of 291 postoperative patients with histologically confirmed and surgically treated grade I meningiomas consented to participation and a total of 455 questionnaires were included for analysis. Patients with meningiomas reported reduced global HRQoL at nearly every 12-month interval with clinically and statistically significant impairments at 12, 48, 108, and 120 months postoperative compared with the normative population (P < 0.05). Meningioma patients at the 12-month interval also reported a reduction of each subdomain of HRQoL assessment (P < 0.05); however, a CMD was only seen in cognitive functioning. Physical, emotional, cognitive, and social subdomains, as well as fatigue and sleep/insomnia, were significantly associated with global HRQoL at the first 12-month interval. Overall, there was no significant correlation between time from surgery and global HRQoL or the subdomain functional or symptom sections of the QLQ-C30. Conclusions Meningioma patients report considerable limitations in HRQoL for more than 120 months after surgery, particularly in cognitive, emotional, and social function, as well as suffering significant fatigue and sleep impairment compared with a normative reference population. The majority of these reported functional impairments and symptoms are strongly associated with global HRQoL and thus can be considered determinants of global HRQoL that if treated, have the potential to improve HRQoL for our meningioma patients. This hypothesis requires future study of targeted interventions to determine their efficacy.

Published
2019
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5. DNA methylation profiling to predict recurrence risk in meningioma: development and validation of a nomogram to optimize clinical management

Author

Nassiri F., Mamatjan Y., Suppiah S., Badhiwala J. H., Mansouri S., Karimi S., Saarela O., Poisson L., Gepfner-Tuma I., Schittenhelm J., Ng H. -K., Noushmehr H., Harter P., Baumgarten P., Weller M., Preusser M., Herold-Mende C., Tatagiba M., Tabatabai G., Sahm F., Von Deimling A., Aldape K., Au K., Barnhartz-Sloan J., Bi W. L., Brastianos P. K., Butowski N., Carlotti C., Cusimano M. D., Dimeco F., Drummond K., Dunn I. F., Galanis E., Giannini C., Goldbrunner R., Griffith B., Hashizume R., Hanemann C. O., Horbinski C., Huang R. Y., James D., Jenkinson M. D., Jungk C., Kaufman T. J., Krischek B., Lachance D., Lafougere C., Lee I., Liu J. C., Malta T. M., Mawrin C., McDermott M., Munoz D., Perry A., Pirouzmand F., Poisson L. M., Pollo B., Raleigh D., Saladino A., Santarius T., Schichor C., Schultz D., Schmidt N. O., Selman W., Sloan A., Spears J., Snyder J., Tirapelli D., Tonn J. C., Tsang D., Vogelbaum M. A., Wen P. Y., Walbert T., Westphal M., Workewych A. M., Zadeh G., Aldape K. D., Nassiri F., Mamatjan Y., Suppiah S., Badhiwala J.H., Mansouri S., Karimi S., Saarela O., Poisson L., Gepfner-Tuma I., Schittenhelm J., Ng H.-K., Noushmehr H., Harter P., Baumgarten P., Weller M., Preusser M., Herold-Mende C., Tatagiba M., Tabatabai G., Sahm F., Von Deimling A., Aldape K., Au K., Barnhartz-Sloan J., Bi W.L., Brastianos P.K., Butowski N., Carlotti C., Cusimano M.D., Dimeco F., Drummond K., Dunn I.F., Galanis E., Giannini C., Goldbrunner R., Griffith B., Hashizume R., Hanemann C.O., Horbinski C., Huang R.Y., James D., Jenkinson M.D., Jungk C., Kaufman T.J., Krischek B., Lachance D., Lafougere C., Lee I., Liu J.C., Malta T.M., Mawrin C., McDermott M., Munoz D., Perry A., Pirouzmand F., Poisson L.M., Pollo B., Raleigh D., Saladino A., Santarius T., Schichor C., Schultz D., Schmidt N.O., Selman W., Sloan A., Spears J., Snyder J., Tirapelli D., Tonn J.C., Tsang D., Vogelbaum M.A., Wen P.Y., Walbert T., Westphal M., Workewych A.M., Zadeh G., and Aldape K.D.

Subjects
Oncology, Cancer Research, medicine.medical_specialty, recurrence, predictor, ESTUDOS DE VALIDAÇÃO, Meningioma, nomogram, Internal medicine, medicine, Biomarkers, Tumor, Meningeal Neoplasms, Humans, Survival rate, Retrospective Studies, Oncotype DX Breast Cancer Assay, business.industry, Hazard ratio, Cancer, Disease Management, Retrospective cohort study, Nomogram, DNA Methylation, medicine.disease, Prognosis, Gene Expression Regulation, Neoplastic, Survival Rate, Clinical research, Basic and Translational Investigations, Neurology (clinical), methylation, Neoplasm Recurrence, Local, business, Follow-Up Studies
Abstract

Background Variability in standard-of-care classifications precludes accurate predictions of early tumor recurrence for individual patients with meningioma, limiting the appropriate selection of patients who would benefit from adjuvant radiotherapy to delay recurrence. We aimed to develop an individualized prediction model of early recurrence risk combining clinical and molecular factors in meningioma. Methods DNA methylation profiles of clinically annotated tumor samples across multiple institutions were used to develop a methylome model of 5-year recurrence-free survival (RFS). Subsequently, a 5-year meningioma recurrence score was generated using a nomogram that integrated the methylome model with established prognostic clinical factors. Performance of both models was evaluated and compared with standard-of-care models using multiple independent cohorts. Results The methylome-based predictor of 5-year RFS performed favorably compared with a grade-based predictor when tested using the 3 validation cohorts (ΔAUC = 0.10, 95% CI: 0.03–0.018) and was independently associated with RFS after adjusting for histopathologic grade, extent of resection, and burden of copy number alterations (hazard ratio 3.6, 95% CI: 1.8–7.2, P < 0.001). A nomogram combining the methylome predictor with clinical factors demonstrated greater discrimination than a nomogram using clinical factors alone in 2 independent validation cohorts (ΔAUC = 0.25, 95% CI: 0.22–0.27) and resulted in 2 groups with distinct recurrence patterns (hazard ratio 7.7, 95% CI: 5.3–11.1, P < 0.001) with clinical implications. Conclusions The models developed and validated in this study provide important prognostic information not captured by previously established clinical and molecular factors which could be used to individualize decisions regarding postoperative therapeutic interventions, in particular whether to treat patients with adjuvant radiotherapy versus observation alone.

Published
2019

6. Advances in multidisciplinary therapy for meningiomas

Author

Brastianos P. K., Galanis E., Butowski N., Chan J. W., Dunn I. F., Goldbrunner R., Herold-Mende C., Ippen F. M., Mawrin C., McDermott M. W., Sloan A., Snyder J., Tabatabai G., Tatagiba M., Tonn J. C., Wen P. Y., Aldape K., Nassiri F., Zadeh G., Jenkinson M. D., Raleigh D. R., Au K., Barnhartz-Sloan J., Bi W. L., Carlotti C., Cusimano M. D., Dimeco F., Drummond K., Giannini C., Griffith B., Hashizume R., Hanemann C. O., Horbinski C., Huang R. Y., James D., Jungk C., Kaufman T. J., Krischek B., Lachance D., Lafougere C., Lee I., Liu J. C., Mamatjan Y., Mansouri A., Munoz D., Noushmehr H., Ng H. -K., Perry A., Pirouzmand F., Poisson L. M., Pollo B., Sahm F., Saladino A., Santarius T., Schichor C., Schultz D., Schmidt N. O., Selman W., Spears J., Suppiah S., Tirapelli D., Tsang D., Vogelbaum M. A., Deimling A. V., Walbert T., Westphal M., Workewych A. M., Brastianos P.K., Galanis E., Butowski N., Chan J.W., Dunn I.F., Goldbrunner R., Herold-Mende C., Ippen F.M., Mawrin C., McDermott M.W., Sloan A., Snyder J., Tabatabai G., Tatagiba M., Tonn J.C., Wen P.Y., Aldape K., Nassiri F., Zadeh G., Jenkinson M.D., Raleigh D.R., Au K., Barnhartz-Sloan J., Bi W.L., Carlotti C., Cusimano M.D., Dimeco F., Drummond K., Giannini C., Griffith B., Hashizume R., Hanemann C.O., Horbinski C., Huang R.Y., James D., Jungk C., Kaufman T.J., Krischek B., Lachance D., Lafougere C., Lee I., Liu J.C., Mamatjan Y., Mansouri A., Munoz D., Noushmehr H., Ng H.-K., Perry A., Pirouzmand F., Poisson L.M., Pollo B., Sahm F., Saladino A., Santarius T., Schichor C., Schultz D., Schmidt N.O., Selman W., Spears J., Suppiah S., Tirapelli D., Tsang D., Vogelbaum M.A., Deimling A.V., Walbert T., Westphal M., and Workewych A.M.

Subjects
Oncology, Cancer Research, medicine.medical_treatment, Supplement Articles, meningioma, Systemic therapy, surgery, 0302 clinical medicine, Meningeal Neoplasms, Trabectedin, Cancer, clinical trial, targeted therapy, Prognosis, Combined Modality Therapy, 3. Good health, 6.1 Pharmaceuticals, 030220 oncology & carcinogenesis, International Consortium on Meningiomas, Patient Safety, Meningioma, medicine.drug, medicine.medical_specialty, Oncology and Carcinogenesis, Antineoplastic Agents, Radiosurgery, 03 medical and health sciences, Internal medicine, medicine, otorhinolaryngologic diseases, Humans, Meningeal Neoplasm, Oncology & Carcinogenesis, neoplasms, business.industry, Neurosciences, Evaluation of treatments and therapeutic interventions, medicine.disease, RADIOTERAPIA, Brain Disorders, nervous system diseases, Clinical trial, Radiation therapy, radiation, Neurology (clinical), Cranial Irradiation, business, 030217 neurology & neurosurgery
Abstract

Surgery has long been established as the first-line treatment for the majority of symptomatic and enlarging meningiomas, and evidence for its success is derived from retrospective case series. Despite surgical resection, a subset of meningiomas display aggressive behavior with early recurrences that are difficult to treat. The decision to radically resect meningiomas and involved structures is balanced against the risk for neurological injury in patients. Radiation therapy has largely been used as a complementary and safe therapeutic strategy in meningiomas with evidence primarily stemming from retrospective, single-institution reports. Two of the first cooperative group studies (RTOG 0539 and EORTC 22042) evaluating the outcomes of adjuvant radiation therapy in higher-risk meningiomas have shown promising preliminary results. Historically, systemic therapy has resulted in disappointing results in meningiomas. However, several clinical trials are under way evaluating the efficacy of chemotherapies, such as trabectedin, and novel molecular agents targeting Smoothened, AKT1, and focal adhesion kinase in patients with recurrent meningiomas.

Published
2019

7. Imaging and diagnostic advances for intracranial meningiomas

Author

Huang R. Y., Bi W. L., Griffith B., Kaufmann T. J., La Fougere C., Schmidt N. O., Tonn J. C., Vogelbaum M. A., Wen P. Y., Aldape K., Nassiri F., Zadeh G., Dunn I. F., Au K., Barnhartz-Sloan J., Brastianos P. K., Butowski N., Carlotti C., Cusimano M. D., Dimeco F., Drummond K., Galanis E., Giannini C., Goldbrunner R., Hashizume R., Hanemann C. O., Herold-Mende C., Horbinski C., James D., Jenkinson M. D., Jungk C., Kaufman T. J., Krischek B., Lachance D., Lafougere C., Lee I., Liu J. C., Mamatjan Y., Mansouri A., Mawrin C., McDermott M., Munoz D., Noushmehr H., Ng H. -K., Perry A., Pirouzmand F., Poisson L. M., Pollo B., Raleigh D., Sahm F., Saladino A., Santarius T., Schichor C., Schultz D., Selman W., Sloan A., Spears J., Snyder J., Suppiah S., Tabatabai G., Tatagiba M., Tirapelli D., Tsang D., Deimling A. V., Walbert T., Westphal M., Workewych A. M., Huang R.Y., Bi W.L., Griffith B., Kaufmann T.J., La Fougere C., Schmidt N.O., Tonn J.C., Vogelbaum M.A., Wen P.Y., Aldape K., Nassiri F., Zadeh G., Dunn I.F., Au K., Barnhartz-Sloan J., Brastianos P.K., Butowski N., Carlotti C., Cusimano M.D., Dimeco F., Drummond K., Galanis E., Giannini C., Goldbrunner R., Hashizume R., Hanemann C.O., Herold-Mende C., Horbinski C., James D., Jenkinson M.D., Jungk C., Kaufman T.J., Krischek B., Lachance D., Lafougere C., Lee I., Liu J.C., Mamatjan Y., Mansouri A., Mawrin C., McDermott M., Munoz D., Noushmehr H., Ng H.-K., Perry A., Pirouzmand F., Poisson L.M., Pollo B., Raleigh D., Sahm F., Saladino A., Santarius T., Schichor C., Schultz D., Selman W., Sloan A., Spears J., Snyder J., Suppiah S., Tabatabai G., Tatagiba M., Tirapelli D., Tsang D., Deimling A.V., Walbert T., Westphal M., and Workewych A.M.

Subjects
Cancer Research, medicine.medical_specialty, Neuroimaging, Supplement Articles, Multimodal Imaging, perfusion, Meningioma, 03 medical and health sciences, 0302 clinical medicine, Medical imaging, medicine, Meningeal Neoplasms, Humans, Meningeal Neoplasm, Radiation treatment planning, medicine.diagnostic_test, business.industry, imaging, Magnetic resonance imaging, medicine.disease, radiology, 3. Good health, Tumor detection, RADIOLOGIA, PET, Oncology, 030220 oncology & carcinogenesis, Radiological weapon, Neurology (clinical), Radiology, business, 030217 neurology & neurosurgery, CT, MRI
Abstract

The archetypal imaging characteristics of meningiomas are among the most stereotypic of all central nervous system (CNS) tumors. In the era of plain film and ventriculography, imaging was only performed if a mass was suspected, and their results were more suggestive than definitive. Following more than a century of technological development, we can now rely on imaging to non-invasively diagnose meningioma with great confidence and precisely delineate the locations of these tumors relative to their surrounding structures to inform treatment planning. Asymptomatic meningiomas may be identified and their growth monitored over time; moreover, imaging routinely serves as an essential tool to survey tumor burden at various stages during the course of treatment, thereby providing guidance on their effectiveness or the need for further intervention. Modern radiological techniques are expanding the power of imaging from tumor detection and monitoring to include extraction of biologic information from advanced analysis of radiological parameters. These contemporary approaches have led to promising attempts to predict tumor grade and, in turn, contribute prognostic data. In this supplement article, we review important current and future aspects of imaging in the diagnosis and management of meningioma, including conventional and advanced imaging techniques using CT, MRI, and nuclear medicine.

Published
2019

10. Erratum: The Immune Landscape of Cancer (Immunity (2018) 48(4) (812–830.e14), (S1074761318301213), (10.1016/j.immuni.2018.03.023))

Author

Thorsson, V., Gibbs, D. L., Brown, S. D., Wolf, D., Bortone, D. S., Ou Yang, T. -H., Porta-Pardo, E., Gao, G. F., Plaisier, C. L., Eddy, J. A., Ziv, E., Culhane, A. C., Paull, E. O., Sivakumar, I. K. A., Gentles, A. J., Malhotra, R., Farshidfar, F., Colaprico, A., Parker, J. S., Mose, L. E., N. S., Vo, Liu, J., Liu, Y., Rader, J., Dhankani, V., Reynolds, S. M., Bowlby, R., Califano, A., Cherniack, A. D., Anastassiou, D., Bedognetti, D., Mokrab, Y., Newman, A. M., Rao, A., Chen, K., Krasnitz, A., Hu, H., Malta, T. M., Noushmehr, H., Pedamallu, C. S., Bullman, S., Ojesina, A. I., Lamb, A., Zhou, W., Shen, H., Choueiri, T. K., Weinstein, J. N., Guinney, J., Saltz, J., Holt, R. A., Rabkin, C. S., Caesar-Johnson, S. J., Demchok, J. A., Felau, I., Kasapi, M., Ferguson, M. L., Hutter, C. M., Sofia, H. J., Tarnuzzer, R., Wang, Z., Yang, L., Zenklusen, J. C., Zhang, J. J., Chudamani, S., Lolla, L., Naresh, R., Pihl, T., Sun, Q., Wan, Y., Wu, Y., Cho, J., Defreitas, T., Frazer, S., Gehlenborg, N., Getz, G., Heiman, D. I., Kim, J., Lawrence, M. S., Lin, P., Meier, S., Noble, M. S., Saksena, G., Voet, D., Zhang, H., Bernard, B., Chambwe, N., Knijnenburg, T., Kramer, R., Leinonen, K., Miller, M., Reynolds, S., Shmulevich, I., Zhang, W., Akbani, R., Broom, B. M., Hegde, A. M., Ju, Z., Kanchi, R. S., Korkut, A., Li, J., Liang, H., Ling, S., Liu, W., Lu, Y., Mills, G. B., K. -S., Ng, Ryan, M., Wang, J., Zhang, J., Abeshouse, A., Armenia, J., Chakravarty, D., Chatila, W. K., de Bruijn, I., Gao, J., Gross, B. E., Heins, Z. J., Kundra, R., La, K., Ladanyi, M., Luna, A., Nissan, M. G., Ochoa, A., Phillips, S. M., Reznik, E., Sanchez-Vega, F., Sander, C., Schultz, N., Sheridan, R., Sumer, S. O., Sun, Y., Taylor, B. S., Anur, P., Peto, M., Spellman, P., Benz, C., Stuart, J. M., Wong, C. K., Yau, C., Hayes, D. N., Wilkerson, M. D., Ally, A., Balasundaram, M., Brooks, D., Carlsen, R., Chuah, E., Dhalla, N., Holt, R., Jones, S. J. M., Kasaian, K., Lee, D., Ma, Y., Marra, M. A., Mayo, M., Moore, R. A., Mungall, A. J., Mungall, K., Robertson, A. G., Sadeghi, S., Schein, J. E., Sipahimalani, P., Tam, A., Thiessen, N., Tse, K., Wong, T., Berger, A. C., Beroukhim, R., Cibulskis, C., Gabriel, S. B., Ha, G., Meyerson, M., Schumacher, S. E., Shih, J., Kucherlapati, M. H., Kucherlapati, R. S., Baylin, S., Cope, L., Danilova, L., Bootwalla, M. S., Lai, P. H., Maglinte, D. T., Van Den Berg, D. J., Weisenberger, D. J., Auman, J. T., Balu, S., Bodenheimer, T., Fan, C., Hoadley, K. A., Hoyle, A. P., Jefferys, S. R., Jones, C. D., Meng, S., Mieczkowski, P. A., Perou, A. H., Perou, C. M., Roach, J., Shi, Y., Simons, J. V., Skelly, T., Soloway, M. G., Tan, D., Veluvolu, U., Fan, H., Hinoue, T., Laird, P. W., Bellair, M., Chang, K., Covington, K., Creighton, C. J., Dinh, H., Doddapaneni, H., Donehower, L. A., Drummond, J., Gibbs, R. A., Glenn, R., Hale, W., Han, Y., Hu, J., Korchina, V., Lee, S., Lewis, L., Li, W., Liu, X., Morgan, M., Morton, D., Muzny, D., Santibanez, J., Sheth, M., Shinbrot, E., Wang, L., Wang, M., Wheeler, D. A., Xi, L., Zhao, F., Hess, J., Appelbaum, E. L., Bailey, M., Cordes, M. G., Ding, L., Fronick, C. C., Fulton, L. A., Fulton, R. S., Kandoth, C., Mardis, E. R., Mclellan, M. D., Miller, C. A., Schmidt, H. K., Wilson, R. K., Crain, D., Curley, E., Gardner, J., Lau, K., Mallery, D., Morris, S., Paulauskis, J., Penny, R., Shelton, C., Shelton, T., Sherman, M., Thompson, E., Yena, P., Bowen, J., Gastier-Foster, J. M., Gerken, M., Leraas, K. M., Lichtenberg, T. M., Ramirez, N. C., Wise, L., Zmuda, E., Corcoran, N., Costello, T., Hovens, C., Carvalho, A. L., de Carvalho, A. C., Fregnani, J. H., Longatto-Filho, A., Reis, R. M., Scapulatempo-Neto, C., Silveira, H. C. S., Vidal, D. O., Burnette, A., Eschbacher, J., Hermes, B., Noss, A., Singh, R., Anderson, M. L., Castro, P. D., Ittmann, M., Huntsman, D., Kohl, B., Le, X., Thorp, R., Andry, C., Duffy, E. R., Lyadov, V., Paklina, O., Setdikova, G., Shabunin, A., Tavobilov, M., Mcpherson, C., Warnick, R., Berkowitz, R., Cramer, D., Feltmate, C., Horowitz, N., Kibel, A., Muto, M., Raut, C. P., Malykh, A., Barnholtz-Sloan, J. S., Barrett, W., Devine, K., Fulop, J., Ostrom, Q. T., Shimmel, K., Wolinsky, Y., Sloan, A. E., De Rose, A., Giuliante, F., Goodman, M., Karlan, B. Y., Hagedorn, C. H., Eckman, J., Harr, J., Myers, J., Tucker, K., Zach, L. A., Deyarmin, B., Kvecher, L., Larson, C., Mural, R. J., Somiari, S., Vicha, A., Zelinka, T., Bennett, J., Iacocca, M., Rabeno, B., Swanson, P., Latour, M., Lacombe, L., Tetu, B., Bergeron, A., Mcgraw, M., Staugaitis, S. M., Chabot, J., Hibshoosh, H., Sepulveda, A., Su, T., Wang, T., Potapova, O., Voronina, O., Desjardins, L., Mariani, O., Roman-Roman, S., Sastre, X., Stern, M. -H., Cheng, F., Signoretti, S., Berchuck, A., Bigner, D., Lipp, E., Marks, J., Mccall, S., Mclendon, R., Secord, A., Sharp, A., Behera, M., Brat, D. J., Chen, A., Delman, K., Force, S., Khuri, F., Magliocca, K., Maithel, S., Olson, J. J., Owonikoko, T., Pickens, A., Ramalingam, S., Shin, D. M., Sica, G., Van Meir, E. G., Eijckenboom, W., Gillis, A., Korpershoek, E., Looijenga, L., Oosterhuis, W., Stoop, H., van Kessel, K. E., Zwarthoff, E. C., Calatozzolo, C., Cuppini, L., Cuzzubbo, S., Dimeco, F., Finocchiaro, G., Mattei, L., Perin, A., Pollo, B., Chen, C., Houck, J., Lohavanichbutr, P., Hartmann, A., Stoehr, C., Stoehr, R., Taubert, H., Wach, S., Wullich, B., Kycler, W., Murawa, D., Wiznerowicz, M., Chung, K., Edenfield, W. J., Martin, J., Baudin, E., Bubley, G., Bueno, R., De Rienzo, A., Richards, W. G., Kalkanis, S., Mikkelsen, T., Scarpace, L., Girard, N., Aymerich, M., Campo, E., Gine, E., Guillermo, A. L., Van Bang, N., Hanh, P. T., Phu, B. D., Tang, Y., Colman, H., Evason, K., Dottino, P. R., Martignetti, J. A., Gabra, H., Juhl, H., Akeredolu, T., Stepa, S., Hoon, D., Ahn, K., Kang, K. J., Beuschlein, F., Breggia, A., Birrer, M., Bell, D., Borad, M., Bryce, A. H., Castle, E., Chandan, V., Cheville, J., Copland, J. A., Farnell, M., Flotte, T., Giama, N., Ho, T., Kendrick, M., Kocher, J. -P., Kopp, K., Moser, C., Nagorney, D., O'Brien, D., O'Neill, B. P., Patel, T., Petersen, G., Que, F., Rivera, M., Roberts, L., Smallridge, R., Smyrk, T., Stanton, M., Thompson, R. H., Torbenson, M., Yang, J. D., Zhang, L., Brimo, F., Ajani, J. A., Gonzalez, A. M. A., Behrens, C., Bondaruk, J., Broaddus, R., Czerniak, B., Esmaeli, B., Fujimoto, J., Gershenwald, J., Guo, C., Lazar, A. J., Logothetis, C., Meric-Bernstam, F., Moran, C., Ramondetta, L., Rice, D., Sood, A., Tamboli, P., Thompson, T., Troncoso, P., Tsao, A., Wistuba, I., Carter, C., Haydu, L., Hersey, P., Jakrot, V., Kakavand, H., Kefford, R., Lee, K., Long, G., Mann, G., Quinn, M., Saw, R., Scolyer, R., Shannon, K., Spillane, A., Stretch, O., Synott, M., Thompson, J., Wilmott, J., Al-Ahmadie, H., Chan, T. A., Ghossein, R., Gopalan, A., Levine, D. A., Reuter, V., Singer, S., Singh, B., Tien, N. V., Broudy, T., Mirsaidi, C., Nair, P., Drwiega, P., Miller, J., Smith, J., Zaren, H., Park, J. -W., Hung, N. P., Kebebew, E., Linehan, W. M., Metwalli, A. R., Pacak, K., Pinto, P. A., Schiffman, M., Schmidt, L. S., Vocke, C. D., Wentzensen, N., Worrell, R., Yang, H., Moncrieff, M., Goparaju, C., Melamed, J., Pass, H., Botnariuc, N., Caraman, I., Cernat, M., Chemencedji, I., Clipca, A., Doruc, S., Gorincioi, G., Mura, S., Pirtac, M., Stancul, I., Tcaciuc, D., Albert, M., Alexopoulou, I., Arnaout, A., Bartlett, J., Engel, J., Gilbert, S., Parfitt, J., Sekhon, H., Thomas, G., Rassl, D. M., Rintoul, R. C., Bifulco, C., Tamakawa, R., Urba, W., Hayward, N., Timmers, H., Antenucci, A., Facciolo, F., Grazi, G., Marino, M., Merola, R., de Krijger, R., Gimenez-Roqueplo, A. -P., Piche, A., Chevalier, S., Mckercher, G., Birsoy, K., Barnett, G., Brewer, C., Farver, C., Naska, T., Pennell, N. A., Raymond, D., Schilero, C., Smolenski, K., Williams, F., Morrison, C., Borgia, J. A., Liptay, M. J., Pool, M., Seder, C. W., Junker, K., Omberg, L., Dinkin, M., Manikhas, G., Alvaro, D., Bragazzi, M. C., Cardinale, V., Carpino, G., Gaudio, E., Chesla, D., Cottingham, S., Dubina, M., Moiseenko, F., Dhanasekaran, R., Becker, K. -F., Janssen, K. -P., Slotta-Huspenina, J., Abdel-Rahman, M. H., Aziz, D., Bell, S., Cebulla, C. M., Davis, A., Duell, R., Elder, J. B., Hilty, J., Kumar, B., Lang, J., Lehman, N. L., Mandt, R., Nguyen, P., Pilarski, R., Rai, K., Schoenfield, L., Senecal, K., Wakely, P., Hansen, P., Lechan, R., Powers, J., Tischler, A., Grizzle, W. E., Sexton, K. C., Kastl, A., Henderson, J., Porten, S., Waldmann, J., Fassnacht, M., Asa, S. L., Schadendorf, D., Couce, M., Graefen, M., Huland, H., Sauter, G., Schlomm, T., Simon, R., Tennstedt, P., Olabode, O., Nelson, M., Bathe, O., Carroll, P. R., Chan, J. M., Disaia, P., Glenn, P., Kelley, R. K., Landen, C. N., Phillips, J., Prados, M., Simko, J., Smith-McCune, K., Vandenberg, S., Roggin, K., Fehrenbach, A., Kendler, A., Sifri, S., Steele, R., Jimeno, A., Carey, F., Forgie, I., Mannelli, M., Carney, M., Hernandez, B., Campos, B., Herold-Mende, C., Jungk, C., Unterberg, A., von Deimling, A., Bossler, A., Galbraith, J., Jacobus, L., Knudson, M., Knutson, T., Ma, D., Milhem, M., Sigmund, R., Godwin, A. K., Madan, R., Rosenthal, H. G., Adebamowo, C., Adebamowo, S. N., Boussioutas, A., Beer, D., Giordano, T., Mes-Masson, A. -M., Saad, F., Bocklage, T., Landrum, L., Mannel, R., Moore, K., Moxley, K., Postier, R., Walker, J., Zuna, R., Feldman, M., Valdivieso, F., Dhir, R., Luketich, J., Pinero, E. M. M., Quintero-Aguilo, M., Carlotti, C. G., Dos Santos, J. S., Kemp, R., Sankarankuty, A., Tirapelli, D., Catto, J., Agnew, K., Swisher, E., Creaney, J., Robinson, B., Shelley, C. S., Godwin, E. M., Kendall, S., Shipman, C., Bradford, C., Carey, T., Haddad, A., Moyer, J., Peterson, L., Prince, M., Rozek, L., Wolf, G., Bowman, R., Fong, K. M., Yang, I., Korst, R., Rathmell, W. K., Fantacone-Campbell, J. L., Hooke, J. A., Kovatich, A. J., Shriver, C. D., Dipersio, J., Drake, B., Govindan, R., Heath, S., Ley, T., Van Tine, B., Westervelt, P., Rubin, M. A., Lee, J. I., Aredes, N. D., Mariamidze, A., Serody, J. S., Demicco, E. G., Disis, M. L., and Vincent, B. G.

Subjects
immune, cancer, methods
Published
2019

13. STR analysis of artificially degraded DNA--results of a collaborative European exercise.

Author

Schneider, Peter M., Bender, Klaus, Mayr, Wolfgang R., Parson, Walther, Hoste, Bernadette, Decorte, Ronny, Cordonnier, Jan, Vanek, Daniel, Morling, Niels, Karjalainen, Matti, Carlotti, C. Marie-Paule, Sabatier, Myriam, Hohoff, Carsten, Schmitter, Hermann, Pflug, Werner, Wenzel, Rainer, Patzelt, Dieter, Lessig, Rudiger, Dobrowolski, Peter, O'Donnell, Geraldine, Garafano, Luciano, Dobosz, Marina, de Knijff, Peter, Mevag, Bente, Pawlowski, Ryszard, Gusmao, Leonor, Vide, Maria Conceicao, Alonso, Antonio, Fernandez, Oscar Garcia, Nicolas, Pilar Sanz, Kihlgreen, Ann, Bar, Walter, Meier, Verena, Teyssier, Anne, Coquoz, Raphael, Brandt, Conxita, Germann, Ursula, Gill, Peter, Hallett, Justine, and Greenhalgh, Matthew

Subjects
Polymerase chain reaction -- Analysis -- Research, Decomposition (Chemistry) -- Analysis -- Research, Allelomorphism -- Research -- Analysis
Abstract

Abstract Degradation of human DNA extracted from forensic stains is, in most cases, the result of a natural process due to the exposure of the stain samples to the environment. [...]

Published
2004

14. Oncogenic signaling pathways in the Cancer Genome Atlas

Author

Sanchez-Vega, F., Mina, M., Armenia, J., Chatila, W. K., Luna, A., La, K. C., Dimitriadoy, S., Liu, D. L., Kantheti, H. S., Saghafinia, S., Chakravarty, D., Daian, F., Gao, Q., Bailey, M. H., Liang, W. -W., Foltz, S. M., Shmulevich, I., Ding, L., Heins, Z., Ochoa, A., Gross, B., Gao, J., Zhang, H., Kundra, R., Kandoth, C., Bahceci, I., Dervishi, L., Doğrusöz, Uğur, Zhou, W., Shen, H., Laird, P. W., Way, G. P., Greene, C. S., Liang, H., Xiao, Y., Wang, C., Iavarone, A., Berger, A. H., Bivona, T. G., Lazar, A. J., Hammer, G. D., Giordano, T., Kwong, L. N., McArthur, G., Huang, C., Tward, A. D., Frederick, M. J., McCormick, F., Meyerson, M., Caesar-Johnson, S. J., Demchok, J. A., Felau, I., Kasapi, M., Ferguson, M. L., Hutter, C. M., Sofia, H. J., Tarnuzzer, R., Wang, Z., Yang, L., Zenklusen, J. C., Zhang, J. J., Chudamani, S., Liu, J., Lolla, L., Naresh, R., Pihl, T., Sun, Q., Wan, Y., Wu, Y., Cho, J., DeFreitas, T., Frazer, S., Gehlenborg, N., Getz, G., Heiman, D. I., Kim, J., Lawrence, M. S., Lin, P., Meier, S., Noble, M. S., Saksena, G., Voet, D., Bernard, B., Chambwe, N., Dhankani, V., Knijnenburg, T., Kramer, R., Leinonen, K., Liu, Y., Miller, M., Reynolds, S., Thorsson, V., Zhang, W., Akbani, R., Broom, B. M., Hegde, A. M., Ju, Z., Kanchi, R. S., Korkut, A., Li, J., Ling, S., Liu W., Lu, Y., Mills, G. B., Ng, K. -S., Rao, A., Ryan, M., Wang, J., Weinstein, J. N., Zhang, J., Abeshouse, A., de, Bruijn, I., Gross, B. E., Heins, Z. J., La, K., Ladanyi, M., Nissan, M. G., Phillips, S. M., Reznik, E., Sander, C., Schultz, N., Sheridan, R., Sumer, S. O., Sun, Y., Taylor, B. S., Anur, P., Peto, M., Spellman, P., Benz, C., Stuart, J. M., Wong, C. K., Yau, C., Hayes, D. N., Parker, J. S., Wilkerson, M. D., Ally, A., Balasundaram, M., Bowlby, R., Brooks, D., Carlsen, R., Chuah, E., Dhalla, N., Holt, R., Jones, S. J. M., Kasaian, K., Lee, D., Ma, Y., Marra, M. A., Mayo, M., Moore, R. A., Mungall, A. J., Mungall, K., Robertson, A. G., Sadeghi, S., Schein, J. E., Sipahimalani, P., Tam, A., Thiessen, N., Tse, K., Wong, T., Berger, A. C., Beroukhim, R., Cherniack, A. D., Cibulskis, C., Gabriel, S. B., Gao, G. F., Ha, G., Schumacher, S. E., Shih, J., Kucherlapati, M. H., Kucherlapati, R. S., Baylin, S., Cope, L., Danilova, L., Bootwalla, M. S., Lai, P. H., Maglinte, D. T., Van, Den, Berg, D. J., Weisenberger, D. J., Auman, J. T., Balu, S., Bodenheimer, T., Fan, C., Hoadley, K. A., Hoyle, A. P., Jefferys, S. R., Jones, C. D., Meng, S., Mieczkowski, P. A., Mose, L. E., Perou, A. H., Perou, C. M., Roach, J., Shi, Y., Simons, J. V., Skelly, T., Soloway, M. G., Tan, D., Veluvolu, U., Fan, H., Hinoue, T., Bellair, M., Chang, K., Covington, K., Creighton, C. J., Dinh, H., Doddapaneni, H., Donehower, L. A., Drummond, J., Gibbs, R. A., Glenn, R., Hale, W., Han, Y., Hu, J., Korchina, V., Lee, S., Lewis, L., Li, W., Liu, X., Morgan, M., Morton, D., Muzny, D., Santibanez, J., Sheth, M., Shinbrot, E., Wang, L., Wang, M., Wheeler, D. A., Xi, L., Zhao, F., Hess, J., Appelbaum, E. L., Bailey, M., Cordes, M. G., Fronick, C. C., Fulton, L. A., Fulton, R. S., Mardis, E. R., McLellan, M. D., Miller, C. A., Schmidt, H. K., Wilson, R. K., Crain, D., Curley, E., Gardner, J., Lau, K., Mallery, D., Morris, S., Paulauskis, J., Penny, R., Shelton, C., Shelton, T., Sherman, M., Thompson, E., Yena, P., Bowen, J., Gastier-Foster, J. M., Gerken, M., Leraas, K. M., Lichtenberg, T. M., Ramirez, N. C., Wise, L., Zmuda, E., Corcoran, N., Costello, T., Hovens, C., Carvalho, A. L., de, Carvalho, A. C., Fregnani, J. H., Longatto-Filho, A., Reis, R. M., Scapulatempo-Neto, C., Silveira, H. C. S., Vidal, D. O., Burnette, A., Eschbacher, J., Hermes, B., Noss, A., Singh, R., Anderson, M. L., Castro, P. D., Ittmann, M., Huntsman, D., Kohl, B., Le, X., Thorp, R., Andry, C., Duffy, E. R., Lyadov, V., Paklina, O., Setdikova, G., Shabunin, A., Tavobilov, M., McPherson, C., Warnick, R., Berkowitz, R., Cramer, D., Feltmate, C., Horowitz, N., Kibel, A., Muto, M., Raut, C. P., Malykh, A., Barnholtz-Sloan, J. S., Barrett, W., Devine, K., Fulop, J., Ostrom, Q. T., Shimmel, K., Wolinsky, Y., Sloan, A. E., De, Rose, A., Giuliante, F., Goodman, M., Karlan, B. Y., Hagedorn, C. H., Eckman, J., Harr, J., Myers, J., Tucker, K., Zach, L. A., Deyarmin, B., Hu, H., Kvecher, L., Larson, C., Mural, R. J., Somiari, S., Vicha, A., Zelinka, T., Bennett, J., Iacocca, M., Rabeno, B., Swanson, P., Latour, M., Lacombe, L., Têtu, B., Bergeron, A., McGraw, M., Staugaitis, S. M., Chabot, J., Hibshoosh, H., Sepulveda, A., Su, T., Wang, T., Potapova, O., Voronina, O., Desjardins, L., Mariani, O., Roman-Roman, S., Sastre, X., Stern, M. -H., Cheng, F., Signoretti, S., Berchuck, A., Bigner, D., Lipp, E., Marks, J., McCall, S., McLendon, R., Secord, A., Sharp, A., Behera, M., Brat, D. J., Chen, A., Delman, K., Force, S., Khuri, F., Magliocca, K., Maithel, S., Olson, J. J., Owonikoko, T., Pickens, A., Ramalingam, S., Shin, D. M., Sica, G., Van, Meir, E. G., Eijckenboom, W., Gillis, A., Korpershoek, E., Looijenga, L., Oosterhuis, W., Stoop, H., van, Kessel, K. E., Zwarthoff, E. C., Calatozzolo, C., Cuppini, L., Cuzzubbo, S., DiMeco, F., Finocchiaro, G., Mattei, L., Perin, A., Pollo, B., Chen, C., Houck, J., Lohavanichbutr, P., Hartmann, A., Stoehr, C., Stoehr, R., Taubert, H., Wach, S., Wullich, B., Kycler, W., Murawa, D., Wiznerowicz, M., Chung, K., Edenfield, W. J., Martin, J., Baudin, E., Bubley, G., Bueno, R., De, Rienzo, A., Richards, W. G., Kalkanis, S., Mikkelsen, T., Noushmehr, H., Scarpace, L., Girard, N., Aymerich, M., Campo, E., Giné, E., Guillermo, A. L., Van, Bang, N., Hanh, P. T., Phu, B. D., Tang, Y., Colman, H., Evason, K., Dottino, P. R., Martignetti, J. A., Gabra, H., Juhl, H., Akeredolu, T., Stepa, S., Hoon, D., Ahn, K., Kang, K. J., Beuschlein, F., Breggia, A., Birrer, M., Bell, D., Borad, M., Bryce, A. H., Castle, E., Chandan, V., Cheville, J., Copland, J. A., Farnell, M., Flotte, T., Giama, N., Ho, T., Kendrick, M., Kocher, J. -P., Kopp, K., Moser, C., Nagorney, D., O'Brien, D., O'Neill, B. P., Patel, T., Petersen, G., Que, F., Rivera, M., Roberts, L., Smallridge, R., Smyrk, T., Stanton, M., Thompson, R. H., Torbenson, M., Yang, J. D., Zhang, L., Brimo, F., Ajani, J. A., Gonzalez, A. M. A., Behrens, C., Bondaruk, J., Broaddus, R., Czerniak, B., Esmaeli, B., Fujimoto, J., Gershenwald, J., Guo, C., Logothetis, C., Meric-Bernstam, F., Moran, C., Ramondetta, L., Rice, D., Sood, A., Tamboli, P., Thompson, T., Troncoso, P., Tsao, A., Wistuba, I., Carter, C., Haydu, L., Hersey, P., Jakrot, V., Kakavand, H., Kefford, R., Lee, K., Long, G., Mann, G., Quinn, M., Saw, R., Scolyer, R., Shannon, K., Spillane, A., Stretch, J., Synott, M., Thompson, J., Wilmott, J., Al-Ahmadie, H., Chan, T. A., Ghossein, R., Gopalan, A., Levine, D. A., Reuter, V., Singer, S., Singh, B., Tien, N. V., Broudy, T., Mirsaidi, C., Nair, P., Drwiega, P., Miller, J., Smith, J., Zaren, H., Park, J. -W., Hung, N. P., Kebebew, E., Linehan, W. M., Metwalli, A. R., Pacak, K., Pinto, P. A., Schiffman, M., Schmidt, L. S., Vocke, C. 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S., Shin D.M., Sica G., Van Meir E.G., Eijckenboom W., Gillis A., Korpershoek E., Looijenga L., Oosterhuis W., Stoop H., van Kessel K.E., Zwarthoff E.C., Calatozzolo C., Cuppini L., Cuzzubbo S., DiMeco F., Finocchiaro G., Mattei L., Perin A., Pollo B., Chen C., Houck J., Lohavanichbutr P., Hartmann A., Stoehr C., Stoehr R., Taubert H., Wach S., Wullich B., Kycler W., Murawa D., Wiznerowicz M., Chung K., Edenfield W.J., Martin J., Baudin E., Bubley G., Bueno R., De Rienzo A., Richards W.G., Kalkanis S., Mikkelsen T., Noushmehr H., Scarpace L., Girard N., Aymerich M., Campo E., Gine E., Guillermo A.L., Van Bang N., Hanh P.T., Phu B.D., Tang Y., Colman H., Evason K., Dottino P.R., Martignetti J.A., Gabra H., Juhl H., Akeredolu T., Stepa S., Hoon D., Ahn K., Kang K.J., Beuschlein F., Breggia A., Birrer M., Bell D., Borad M., Bryce A.H., Castle E., Chandan V., Cheville J., Copland J.A., Farnell M., Flotte T., Giama N., Ho T., Kendrick M., Kocher J.-P., Kopp K., Moser C., Nagorney D., O'Brien D., O'Neill B.P., Patel T., Petersen G., Que F., Rivera M., Roberts L., Smallridge R., Smyrk T., Stanton M., Thompson R.H., Torbenson M., Yang J.D., Zhang L., Brimo F., Ajani J.A., Gonzalez A.M.A., Behrens C., Bondaruk J., Broaddus R., Czerniak B., Esmaeli B., Fujimoto J., Gershenwald J., Guo C., Logothetis C., Meric-Bernstam F., Moran C., Ramondetta L., Rice D., Sood A., Tamboli P., Thompson T., Troncoso P., Tsao A., Wistuba I., Carter C., Haydu L., Hersey P., Jakrot V., Kakavand H., Kefford R., Lee K., Long G., Mann G., Quinn M., Saw R., Scolyer R., Shannon K., Spillane A., Stretch J., Synott M., Thompson J., Wilmott J., Al-Ahmadie H., Chan T.A., Ghossein R., Gopalan A., Levine D.A., Reuter V., Singer S., Singh B., Tien N.V., Broudy T., Mirsaidi C., Nair P., Drwiega P., Miller J., Smith J., Zaren H., Park J.-W., Hung N.P., Kebebew E., Linehan W.M., Metwalli A.R., Pacak K., Pinto P.A., Schiffman M., Schmidt L.S., Vocke C.D., Wentzensen N., Worrell R., Yang H., Moncrieff M., Goparaju C., Melamed J., Pass H., Botnariuc N., Caraman I., Cernat M., Chemencedji I., Clipca A., Doruc S., Gorincioi G., Mura S., Pirtac M., Stancul I., Tcaciuc D., Albert M., Alexopoulou I., Arnaout A., Bartlett J., Engel J., Gilbert S., Parfitt J., Sekhon H., Thomas G., Rassl D.M., Rintoul R.C., Bifulco C., Tamakawa R., Urba W., Hayward N., Timmers H., Antenucci A., Facciolo F., Grazi G., Marino M., Merola R., de Krijger R., Gimenez-Roqueplo A.-P., Piche A., Chevalier S., McKercher G., Birsoy K., Barnett G., Brewer C., Farver C., Naska T., Pennell N.A., Raymond D., Schilero C., Smolenski K., Williams F., Morrison C., Borgia J.A., Liptay M.J., Pool M., Seder C.W., Junker K., Omberg L., Dinkin M., Manikhas G., Alvaro D., Bragazzi M.C., Cardinale V., Carpino G., Gaudio E., Chesla D., Cottingham S., Dubina M., Moiseenko F., Dhanasekaran R., Becker K.-F., Janssen K.-P., Slotta-Huspenina J., Abdel-Rahman M.H., Aziz D., Bell S., Cebulla C.M., Davis A., Duell R., Elder J.B., Hilty J., Kumar B., Lang J., Lehman N.L., Mandt R., Nguyen P., Pilarski R., Rai K., Schoenfield L., Senecal K., Wakely P., Hansen P., Lechan R., Powers J., Tischler A., Grizzle W.E., Sexton K.C., Kastl A., Henderson J., Porten S., Waldmann J., Fassnacht M., Asa S.L., Schadendorf D., Couce M., Graefen M., Huland H., Sauter G., Schlomm T., Simon R., Tennstedt P., Olabode O., Nelson M., Bathe O., Carroll P.R., Chan J.M., Disaia P., Glenn P., Kelley R.K., Landen C.N., Phillips J., Prados M., Simko J., Smith-McCune K., VandenBerg S., Roggin K., Fehrenbach A., Kendler A., Sifri S., Steele R., Jimeno A., Carey F., Forgie I., Mannelli M., Carney M., Hernandez B., Campos B., Herold-Mende C., Jungk C., Unterberg A., von Deimling A., Bossler A., Galbraith J., Jacobus L., Knudson M., Knutson T., Ma D., Milhem M., Sigmund R., Godwin A.K., Madan R., Rosenthal H.G., Adebamowo C., Adebamowo S.N., Boussioutas A., Beer D., Mes-Masson A.-M., Saad F., Bocklage T., Landrum L., Mannel R., Moore K., Moxley K., Postier R., Walker J., Zuna R., Feldman M., Valdivieso F., Dhir R., Luketich J., Pinero E.M.M., Quintero-Aguilo M., Carlotti C.G., Dos Santos J.S., Kemp R., Sankarankuty A., Tirapelli D., Catto J., Agnew K., Swisher E., Creaney J., Robinson B., Shelley C.S., Godwin E.M., Kendall S., Shipman C., Bradford C., Carey T., Haddad A., Moyer J., Peterson L., Prince M., Rozek L., Wolf G., Bowman R., Fong K.M., Yang I., Korst R., Rathmell W.K., Fantacone-Campbell J.L., Hooke J.A., Kovatich A.J., Shriver C.D., DiPersio J., Drake B., Govindan R., Heath S., Ley T., Van Tine B., Westervelt P., Rubin M.A., Lee J.I., Aredes N.D., Mariamidze A., Van Allen E.M., and Ciriello G.

Subjects
0301 basic medicine, cancer genome atlas, cancer genomics, combination therapy, pan-cancer, PanCanAtlas, precision oncology, signaling pathways, TCGA, therapeutics, whole exome sequencing, Signaling pathways, Somatic cell, Wnt Protein, Cancer Genome Atlas Research Network, Biochemistry, Medical and Health Sciences, Phosphatidylinositol 3-Kinases, Transforming Growth Factor beta, Neoplasms, Databases, Genetic, LS2_1, Cancer genomics, LS4_6, 610 Medicine & health, 11 Medical and Health Sciences, Cancer, biology, Wnt signaling pathway, cancer genomic, Precision oncology, Biological Sciences, Cell cycle, DNA methylation, Signal transduction, CICLO CELULAR, Life Sciences & Biomedicine, Genes, Neoplasm, Humans, Neoplasms/genetics, Neoplasms/pathology, Phosphatidylinositol 3-Kinases/genetics, Phosphatidylinositol 3-Kinases/metabolism, Signal Transduction/genetics, Transforming Growth Factor beta/genetics, Transforming Growth Factor beta/metabolism, Tumor Suppressor Protein p53/genetics, Tumor Suppressor Protein p53/metabolism, Wnt Proteins/genetics, Wnt Proteins/metabolism, Biotechnology, Human, Signal Transduction, signaling pathway, EXPRESSION, Biochemistry & Molecular Biology, GENES, Pan-cancer, Therapeutics, General Biochemistry, Genetics and Molecular Biology, NO, Databases, 03 medical and health sciences, Genetic, Genetics, Combination therapy, Protein kinase B, Gene, SIGNATURES, Cancer genome atlas, Science & Technology, LANDSCAPE, MUTATIONS, Biochemistry, Genetics and Molecular Biology(all), Human Genome, Whole exome sequencing, Cell Biology, Transforming growth factor beta, cancer genome atla, 06 Biological Sciences, COMPREHENSIVE MOLECULAR CHARACTERIZATION, Wnt Proteins, therapeutic, Good Health and Well Being, 030104 developmental biology, Genes, PanCanAtla, biology.protein, Cancer research, Neoplasm, Phosphatidylinositol 3-Kinase, Tumor Suppressor Protein p53, Digestive Diseases, Genetics and Molecular Biology(all), Developmental Biology
Abstract

Genetic alterations in signaling pathways that control cell-cycle progression, apoptosis, and cell growth are common hallmarks of cancer, but the extent, mechanisms, and co-occurrence of alterations in these pathways differ between individual tumors and tumor types. Using mutations, copy-number changes, mRNA expression, gene fusions and DNA methylation in 9,125 tumors profiled by The Cancer Genome Atlas (TCGA), we analyzed the mechanisms and patterns of somatic alterations in ten canonical pathways: cell cycle, Hippo, Myc, Notch, Nrf2, PI-3-Kinase/Akt, RTK-RAS, TGFβ signaling, p53 and β-catenin/Wnt. We charted the detailed landscape of pathway alterations in 33 cancer types, stratified into 64 subtypes, and identified patterns of co-occurrence and mutual exclusivity. Eighty-nine percent of tumors had at least one driver alteration in these pathways, and 57% percent of tumors had at least one alteration potentially targetable by currently available drugs. Thirty percent of tumors had multiple targetable alterations, indicating opportunities for combination therapy. An integrated analysis of genetic alterations in 10 signaling pathways in >9,000 tumors profiled by TCGA highlights significant representation of individual and co-occurring actionable alterations in these pathways, suggesting opportunities for targeted and combination therapies. Michael Seiler, Peter G. Smith, Ping Zhu, Silvia Buonamici, and Lihua Yu are employees of H3 Biomedicine, Inc. Parts of this work are the subject of a patent application: WO2017040526 titled “Splice variants associated with neomorphic sf3b1 mutants.” Shouyoung Peng, Anant A. Agrawal, James Palacino, and Teng Teng are employees of H3 Biomedicine, Inc. Andrew D. Cherniack, Ashton C. Berger, and Galen F. Gao receive research support from Bayer Pharmaceuticals. Gordon B. Mills serves on the External Scientific Review Board of Astrazeneca. Anil Sood is on the Scientific Advisory Board for Kiyatec and is a shareholder in BioPath. Jonathan S. Serody receives funding from Merck, Inc. Kyle R. Covington is an employee of Castle Biosciences, Inc. Preethi H. Gunaratne is founder, CSO, and shareholder of NextmiRNA Therapeutics. Christina Yau is a part-time employee/consultant at NantOmics. Franz X. Schaub is an employee and shareholder of SEngine Precision Medicine, Inc. Carla Grandori is an employee, founder, and shareholder of SEngine Precision Medicine, Inc. Robert N. Eisenman is a member of the Scientific Advisory Boards and shareholder of Shenogen Pharma and Kronos Bio. Daniel J. Weisenberger is a consultant for Zymo Research Corporation. Joshua M. Stuart is the founder of Five3 Genomics and shareholder of NantOmics. Marc T. Goodman receives research support from Merck, Inc. Andrew J. Gentles is a consultant for Cibermed. Charles M. Perou is an equity stock holder, consultant, and Board of Directors member of BioClassifier and GeneCentric Diagnostics and is also listed as an inventor on patent applications on the Breast PAM50 and Lung Cancer Subtyping assays. Matthew Meyerson receives research support from Bayer Pharmaceuticals; is an equity holder in, consultant for, and Scientific Advisory Board chair for OrigiMed; and is an inventor of a patent for EGFR mutation diagnosis in lung cancer, licensed to LabCorp. Eduard Porta-Pardo is an inventor of a patent for domainXplorer. Han Liang is a shareholder and scientific advisor of Precision Scientific and Eagle Nebula. Da Yang is an inventor on a pending patent application describing the use of antisense oligonucleotides against specific lncRNA sequence as diagnostic and therapeutic tools. Yonghong Xiao was an employee and shareholder of TESARO, Inc. Bin Feng is an employee and shareholder of TESARO, Inc. Carter Van Waes received research funding for the study of IAP inhibitor ASTX660 through a Cooperative Agreement between NIDCD, NIH, and Astex Pharmaceuticals. Raunaq Malhotra is an employee and shareholder of Seven Bridges, Inc. Peter W. Laird serves on the Scientific Advisory Board for AnchorDx. Joel Tepper is a consultant at EMD Serono. Kenneth Wang serves on the Advisory Board for Boston Scientific, Microtech, and Olympus. Andrea Califano is a founder, shareholder, and advisory board member of DarwinHealth, Inc. and a shareholder and advisory board member of Tempus, Inc. Toni K. Choueiri serves as needed on advisory boards for Bristol-Myers Squibb, Merck, and Roche. Lawrence Kwong receives research support from Array BioPharma. Sharon E. Plon is a member of the Scientific Advisory Board for Baylor Genetics Laboratory. Beth Y. Karlan serves on the Advisory Board of Invitae.

Published
2018
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16. Sudan Black B treatment reduces autofluorescence and improves resolution of in situ hybridization specific fluorescent signals of brain sections

Author

Viviane de Cássia Oliveira, Carrara, R. C. V., Simoes, D. L. C., Saggioro, F. P., Carlotti, C. G., Covas, D. T., and Neder, L.

Subjects
616 - Patología. Medicina clínica. Oncología, Autofluorescence, Human brain
Abstract

Interference by autofluorescence is one of the major concerns of immunofluorescence analysis of in situ hybridization-based diagnostic assays. We present a useful technique that reduces autofluorescent background without affecting the tissue integrity or direct immunofluorescence signals in brain sections. Using six different protocols, such as ammonia/ethanol, Sudan Black B (SBB) in 70% ethanol, photobleaching with UV light and different combinations of them in both formalin-fixed paraffin-embedded and frozen human brain tissue sections, we have found that tissue treatment of SBB in a concentration of 0.1% in 70% ethanol is the best approach to reduce/eliminate tissue autofluorescence and background, while preserving the specific fluorescence hybridization signals. This strategy is a feasible, non-time consuming method that provides a reasonable compromise between total reduction of the tissue autofluorescence and maintenance of specific fluorescent labels.

Published
2010

17. Mood Disorder Due to a General Medical Condition with Manic Features

Author

Oliveira, J. P., Morais, S. L., Araújo, D., Carlotti, C. G.Jr., Colli, B. O., Crippa, J. A. S., and Cecílio Hallak, J. E.

Subjects
Article Subject
Abstract

This case report describes a patient with manic and psychotic symptoms who had a history of neurocysticercosis and presented with an episode of hypertensive hydrocephalus in 2003. Despite her history, she was initially treated for primary psychiatric disease.

Published
2009
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18. Inhibition of NF-κB by Dehydroxymethylepoxyquinomicin Suppresses Invasion and Synergistically Potentiates Temozolomide and γ-Radiation Cytotoxicity in Glioblastoma Cells

Author

Brassesco, M. S., primary, Roberto, G. M., additional, Morales, A. G., additional, Oliveira, J. C., additional, Delsin, L. E. A., additional, Pezuk, J. A., additional, Valera, E. T., additional, Carlotti, C. G., additional, Rego, E. M., additional, de Oliveira, H. F., additional, Scrideli, C. A., additional, Umezawa, K., additional, and Tone, L. G., additional

Published
2013
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19. STR analysis of artificially degraded DNA-results of a collaborative European exercise

Author

Schneider, Peter M, Bender, Klaus, Mayr, Wolfgang R, Parson, Walther, Hoste, Bernadette, Decorte, Ronny, Cordonnier, Jan, Vanek, Daniel, Morling, Niels, Karjalainen, Matti, Marie-Paule Carlotti, C, Sabatier, Myriam, Hohoff, Carsten, Schmitter, Hermann, Pflug, Werner, Wenzel, Rainer, Patzelt, Dieter, Lessig, Rüdiger, Dobrowolski, Peter, O'Donnell, Geraldine, Garafano, Luciano, Dobosz, Marina, De Knijff, Peter, Mevag, Bente, Pawlowski, Ryszard, Gusmão, Leonor, Conceicao Vide, Maria, Alonso Alonso, Antonio, García Fernández, Oscar, Sanz Nicolás, Pilar, Kihlgreen, Ann, Bär, Walter, Meier, Verena, Teyssier, Anne, Coquoz, Raphael, Brandt, Conxita, Germann, Ursula, Gill, Peter, Hallett, Justine, Greenhalgh, Matthew, Schneider, Peter M, Bender, Klaus, Mayr, Wolfgang R, Parson, Walther, Hoste, Bernadette, Decorte, Ronny, Cordonnier, Jan, Vanek, Daniel, Morling, Niels, Karjalainen, Matti, Marie-Paule Carlotti, C, Sabatier, Myriam, Hohoff, Carsten, Schmitter, Hermann, Pflug, Werner, Wenzel, Rainer, Patzelt, Dieter, Lessig, Rüdiger, Dobrowolski, Peter, O'Donnell, Geraldine, Garafano, Luciano, Dobosz, Marina, De Knijff, Peter, Mevag, Bente, Pawlowski, Ryszard, Gusmão, Leonor, Conceicao Vide, Maria, Alonso Alonso, Antonio, García Fernández, Oscar, Sanz Nicolás, Pilar, Kihlgreen, Ann, Bär, Walter, Meier, Verena, Teyssier, Anne, Coquoz, Raphael, Brandt, Conxita, Germann, Ursula, Gill, Peter, Hallett, Justine, and Greenhalgh, Matthew

Abstract

Udgivelsesdato: 2004-Jan-28, Degradation of human DNA extracted from forensic stains is, in most cases, the result of a natural process due to the exposure of the stain samples to the environment. Experiences with degraded DNA from casework samples show that every sample may exhibit different properties in this respect, and that it is difficult to systematically assess the performance of routinely used typing systems for the analysis of degraded DNA samples. Using a batch of artificially degraded DNA with an average fragment size of approx. 200 bp a collaborative exercise was carried out among 38 forensic laboratories from 17 European countries. The results were assessed according to correct allele detection, peak height and balance as well as the occurrence of artefacts. A number of common problems were identified based on these results such as strong peak imbalance in heterozygous genotypes for the larger short tandem repeat (STR) fragments after increased PCR cycle numbers, artefact signals and allelic drop-out. Based on the observations, strategies are discussed to overcome these problems. The strategies include careful balancing of the amount of template DNA and the PCR cycle numbers, the reaction volume and the amount of Taq polymerase. Furthermore, a careful evaluation of the results of the fragment analysis and of automated allele calling is necessary to identify the correct alleles and avoid artefacts.

Published
2004

33. Cortical malformations are associated with a rare polymorphism of cellular prion protein

Author

Walz, R., primary, Castro, R. M.R.P.S., additional, Landemberger, M. C., additional, Velasco, T. R., additional, Terra-Bustamante, V. C., additional, Bastos, A. C., additional, Bianchin, M., additional, Wichert-Ana, L., additional, Araújo, D., additional, Alexandre, V., additional, Santos, A. C., additional, Machado, H. R., additional, Carlotti, C. G., additional, Brentani, R. R., additional, Martins, V. R., additional, and Sakamoto, A. C., additional

Published
2004
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35. Surgical outcome in mesial temporal sclerosis correlates with prion protein gene variant

Author

Walz, R., primary, Castro, R. M.R.P.S., additional, Velasco, T. R., additional, Alexandre, V., additional, Lopes, M. H., additional, Leite, J. P., additional, Santos, A. C., additional, Assirati, J. A., additional, Wichert-Ana, L., additional, Terra-Bustamante, V. C., additional, Bianchin, M. M., additional, Maciag, P. C., additional, Ribeiro, K. B., additional, Guarnieri, R., additional, Araujo, D., additional, Cabalero, O., additional, Moura, R., additional, Salim, A. C.M., additional, Kindlmann, K., additional, Landemberger, M. C., additional, Marques, W., additional, Fernandes, R. M.F., additional, Serafini, L. N., additional, Machado, H. R., additional, Carlotti, C. G., additional, Brentani, R. R., additional, Sakamoto, A. C., additional, and Martins, V. R., additional

Published
2003
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40. Transcriptional changes in U343 MG-a glioblastoma cell line exposed to ionizing radiation.

Author

Bassi, C. L., Mello, S. S., Cardoso, R. S., Godoy, P. D. V., Fachin, A. L., Junta, C. M., Sandrin-Garcia, P., Carlotti, C. G., Falcão, R. P., Donadi, E. A., Passos, G. A. S., and Sakamoto-Hojo, E. T.

Subjects
GLIOBLASTOMA multiforme, GLIOMAS, CELL lines, GENE expression, MOLECULAR cloning, GENETIC algorithms, BIOLOGICAL transport, DNA repair, CELL adhesion
Abstract

Glioblastoma multiforme (GBM) is a highly invasive and radioresistant brain tumor. Aiming to study how glioma cells respond to ?-rays in terms of biological processes involved in cellular responses, we performed experiments at cellular context and gene expression analysis in U343-MG-a GBM cells irradiated with 1 Gy and collected at 6 h post-irradiation. The survival rate was approximately 61% for 1 Gy and was completely reduced at 16 Gy. By performing the microarray technique, 859 cDNA clones were analyzed. The Significance Analysis of Microarray algorithm indicated 196 significant expressed genes (false discovery rate (FDR) = 0.42%): 67 down-regulated and 97 up-regulated genes, which belong to several classes: metabolism, adhesion/cytoskeleton, signal transduction, cell cycle/apoptosis, membrane transport, DNA repair/DNA damage signaling, transcription factor, intracellular signaling, and RNA processing. Differential expression patterns of five selected genes (HSPA9B, INPP5A, PIP5K1A, FANCG, and TPP2) observed by the microarray analysis were further confirmed by the quantitative real time RT-PCR method, which demonstrated an up-regulation status of those genes. These results indicate a broad spectrum of biological processes (which may reflect the radio-resistance of U343 cells) that were altered in irradiated glioma cells, so as to guarantee cell survival. [ABSTRACT FROM AUTHOR]

Published
2008
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41. Phosphoproteomic Analysis of Synaptosomes from Human Cerebral Cortex

Author

DeGiorgis, J. A., Jaffe, H., Moreira, J. E., Carlotti, C. G., Jr., Leite, J. P., Pant, H. C., and Dosemeci, A.

Abstract

Protein phosphorylation is a crucial post-translational modification mechanism in the regulation of synaptic organization and function. Here, we analyzed synaptosome fractions from human cerebral cortex obtained during therapeutic surgery. To minimize changes in the phosphorylation state of proteins, the tissue was homogenized within two minutes of excision. Synaptosomal proteins were digested with trypsin and phosphopeptides were isolated by immobilized metal affinity chromatography and analyzed by liquid chromatography and tandem mass spectrometry. The method allowed the detection of residues on synaptic proteins that were presumably phosphorylated in the intact cell, including synapsin 1, syntaxin 1, and SNIP, PSD-93, NCAM, GABA-B receptor, chaperone molecules, and protein kinases. Some of the residues identified are the same or homologous to sites that had been previously described to be phosphorylated in mammals whereas others appear to be novel sites which, to our knowledge, have not been reported previously. The study shows that new phosphoproteomic strategies can be used to analyze subcellular fractions from small amounts of tissue for the identification of phosphorylated residues for research and potentially for diagnostic purposes. Keywords: LC−MS/MS • IMAC • mass spectrometry • protein phosphorylation • phosphoproteomics • synaptosome • synaptic • synataxin • SNIP • GABA-B

Published
2005

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