4 results on '"Alexander Fortuna"'
Search Results
2. Tumor genomic, transcriptomic, and immune profiling characterizes differential response to first‐line platinum chemotherapy in high grade serous ovarian cancer
- Author
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Johanne I. Weberpals, Trevor J. Pugh, Paola Marco‐Casanova, Glenwood D. Goss, Natalie Andrews Wright, Prisni Rath, Jonathon Torchia, Alexander Fortuna, Gemma N. Jones, Martine P. Roudier, Laurence Bernard, Bryan Lo, Dax Torti, Alberto Leon, Kayla Marsh, Darren Hodgson, Marc Duciaume, William J. Howat, Natalia Lukashchuk, Stanley E. Lazic, Doreen Whelan, and Harmanjatinder S. Sekhon
- Subjects
genomic profiling ,high grade serous ,immune profiling ,ovarian carcinoma ,platinum resistance ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background In high grade serous ovarian cancer (HGSOC), there is a spectrum of sensitivity to first line platinum‐based chemotherapy. This study molecularly characterizes HGSOC patients from two distinct groups of chemotherapy responders (good vs. poor). Methods Following primary debulking surgery and intravenous carboplatin/paclitaxel, women with stage III–IV HGSOC were grouped by response. Patients in the good response (GR) and poor response (PR) groups respectively had a progression‐free intervals (PFI) of ≥12 and ≤6 months. Analysis of surgical specimens interrogated genomic and immunologic features using whole exome sequencing. RNA‐sequencing detected gene expression outliers and inference of immune infiltrate, with validation by targeted NanoString arrays. PD‐L1 expression was scored by immunohistochemistry (IHC). Results A total of 39 patient samples were analyzed (GR = 20; PR = 19). Median PFI for GR and PR patient cohorts was 32 and 3 months, respectively. GR tumors were enriched for loss‐of‐function BRCA2 mutations and had a significantly higher nonsynonymous mutation rate compared to PR tumors (p = 0.001). Samples from the PR cohort were characterized by mutations in MGA and RAD51B and trended towards a greater rate of amplification of PIK3CA, MECOM, and ATR in comparison to GR tumors. Gene expression analysis by NanoString correlated increased PARP4 with PR and increased PD‐L1 and EMSY with GR. There was greater tumor immune cell infiltration and higher immune cell PD‐L1 protein expression in the GR group. Conclusions Our research demonstrates that tumors from HGSOC patients responding poorly to first line chemotherapy have a distinct molecular profile characterized by actionable drug targets including PARP4.
- Published
- 2021
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3. Tumor genomic, transcriptomic, and immune profiling characterizes differential response to first‐line platinum chemotherapy in high grade serous ovarian cancer
- Author
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Natalie Andrews Wright, Prisni Rath, Trevor J. Pugh, Glenwood D. Goss, Gemma N Jones, Harmanjatinder S. Sekhon, Natalia Lukashchuk, Kayla Marsh, Bryan Lo, Paola Marco-Casanova, Laurence Bernard, William J. Howat, Dax Torti, Jonathon Torchia, Marc Duciaume, Alberto Leon, Darren Hodgson, Stanley E. Lazic, Johanne I Weberpals, Doreen Whelan, Alexander Fortuna, and Martine P. Roudier
- Subjects
0301 basic medicine ,Oncology ,Cancer Research ,Time Factors ,medicine.medical_treatment ,Genes, BRCA2 ,Genes, BRCA1 ,Ataxia Telangiectasia Mutated Proteins ,B7-H1 Antigen ,Carboplatin ,chemistry.chemical_compound ,0302 clinical medicine ,Ovarian carcinoma ,Antineoplastic Combined Chemotherapy Protocols ,Medicine ,RC254-282 ,Exome sequencing ,Original Research ,Aged, 80 and over ,Ovarian Neoplasms ,immune profiling ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Nuclear Proteins ,Cytoreduction Surgical Procedures ,Middle Aged ,Debulking ,platinum resistance ,Progression-Free Survival ,Neoplasm Proteins ,Treatment Outcome ,Paclitaxel ,030220 oncology & carcinogenesis ,Immunohistochemistry ,Female ,genomic profiling ,Adult ,medicine.medical_specialty ,MECOM ,Class I Phosphatidylinositol 3-Kinases ,03 medical and health sciences ,Internal medicine ,Exome Sequencing ,Humans ,Radiology, Nuclear Medicine and imaging ,Aged ,Retrospective Studies ,Chemotherapy ,high grade serous ,business.industry ,Gene Expression Profiling ,Gene Amplification ,Clinical Cancer Research ,Genes, p53 ,MDS1 and EVI1 Complex Locus Protein ,Cystadenocarcinoma, Serous ,ovarian carcinoma ,Repressor Proteins ,030104 developmental biology ,chemistry ,Mutation ,business ,Transcriptome - Abstract
Background In high grade serous ovarian cancer (HGSOC), there is a spectrum of sensitivity to first line platinum‐based chemotherapy. This study molecularly characterizes HGSOC patients from two distinct groups of chemotherapy responders (good vs. poor). Methods Following primary debulking surgery and intravenous carboplatin/paclitaxel, women with stage III–IV HGSOC were grouped by response. Patients in the good response (GR) and poor response (PR) groups respectively had a progression‐free intervals (PFI) of ≥12 and ≤6 months. Analysis of surgical specimens interrogated genomic and immunologic features using whole exome sequencing. RNA‐sequencing detected gene expression outliers and inference of immune infiltrate, with validation by targeted NanoString arrays. PD‐L1 expression was scored by immunohistochemistry (IHC). Results A total of 39 patient samples were analyzed (GR = 20; PR = 19). Median PFI for GR and PR patient cohorts was 32 and 3 months, respectively. GR tumors were enriched for loss‐of‐function BRCA2 mutations and had a significantly higher nonsynonymous mutation rate compared to PR tumors (p = 0.001). Samples from the PR cohort were characterized by mutations in MGA and RAD51B and trended towards a greater rate of amplification of PIK3CA, MECOM, and ATR in comparison to GR tumors. Gene expression analysis by NanoString correlated increased PARP4 with PR and increased PD‐L1 and EMSY with GR. There was greater tumor immune cell infiltration and higher immune cell PD‐L1 protein expression in the GR group. Conclusions Our research demonstrates that tumors from HGSOC patients responding poorly to first line chemotherapy have a distinct molecular profile characterized by actionable drug targets including PARP4., In patients with suboptimally‐debulked, advanced high grade serous ovarian cancer (HGSOC), the spectrum of responses to first line platinum‐based chemotherapy (PtC) vary from durable to non‐existent, highlighting an unmet medical need for those with poor responses. Our study molecularly characterizes a cohort of HGSOC patients with distinct responses, either good or poor, to PtC. The good and poor responders have median progression‐free intervals of 32 and 3 months, respectively, and molecular analysis of tumors identifies differences in DNA damage response pathways and immunity, namely, tumors from poor responders to first line PtC have a distinct molecular profile characterized by actionable drug targets including PARP4.
- Published
- 2021
4. Draft Genome Sequences of Four Clinical Legionella pneumophila Isolates from Ontario, Canada
- Author
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Alexander Fortuna, Nahuel Fittipaldi, Gustavo V. Mallo, Christine Frantz, Ricardo Ramnarine, and Aimin Li
- Subjects
0301 basic medicine ,Genetics ,biology ,Outbreak ,biology.organism_classification ,bacterial infections and mycoses ,Legionella pneumophila ,Genome ,respiratory tract diseases ,03 medical and health sciences ,030104 developmental biology ,bacteria ,Typing methods ,Prokaryotes ,Molecular Biology ,Ontario canada - Abstract
Legionella pneumophila outbreak investigations require the development of reliable typing methods to better understand the genetic relationships of the isolates involved. Here, we report the draft genome sequences of four clinical Legionella pneumophila isolates obtained between 2000 and 2012 in Ontario, Canada.
- Published
- 2018
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