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Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome caused by germline variants in the APC gene, leading to the development of numerous colorectal polyps and significantly increases the risk of colorectal cancer. A diagnosis is typically made using colonoscopy, and genetic testing can assist in patient surveillance and carrier identification. Recent advances include the use of whole-genome array comparative genomic hybridization (a-CGH), which provides better resolution of genetic imbalances. We aimed to explore the specific features of FAP patients with whole APC gene deletions using high-resolution a-CGH and to compare patient characteristics. Two polyposis patients with whole APC deletions were identified, and the lost genetic sizes ranged from 0.3-1.1 Mb. Nervous abnormalities were a characteristic symptom in a patient with a 1.1 Mb loss. A patient with an approximately 0.3 Mb loss, which included the entire APC gene, presented a polyposis phenotype without intellectual disability. The comparison of genetic losses, with or without intellectual disability, revealed 7 genetic changes. Consequently, EPB41L4A is a candidate gene associated with the neurogenic phenotype., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Acute myeloid leukemia (AML) is an aggressive hematological malignancy with genetic alterations. The FMS-like tyrosine kinase 3 (FLT3) gene is frequently mutated in adult de novo AML, with two types of mutations: internal tandem duplication (ITD) and point mutations in the tyrosine kinase domain. This study aimed to investigate the impact of FLT3 inhibitors and hematopoietic cell transplantation (HCT) on survival outcomes in patients with FLT3-ITD AML in a real-world setting. We retrospectively analyzed 139 patients with FLT3-ITD-positive AML between 2012 and 2021. The median age was 63 years. In the propensity score-matched cohort, FLT3 inhibitors improved overall survival (OS) compared with patients treated without FLT3 inhibitors (3-year OS: 33.7% vs. 25.8%, p = 0.021). Patients who underwent HCT had superior outcomes to those without HCT (3-year OS: 45.3% vs. 2.2%, p < 0.0001). The combination of FLT3 inhibitors and HCT resulted in the highest OS and relapse-free survival (RFS) rates (3-year OS: 62.4%; 3-year RFS: 44.4%). Disease status before transplantation did not predict the prognosis, but use of FLT3 inhibitors increased survival in patients without complete remission before HCT. These results demonstrate the clinical impact of FLT3 inhibitors on survival outcomes in patients with FLT3-ITD-positive AML, particularly when combined with HCT. FLT3 inhibitors can improve the prognosis of AML with FLT3 mutations, especially in patients who undergo HCT., Competing Interests: Declarations. Ethical approval: All procedures involving human participants were in accordance with the ethical standards of institutional research committees, national guidelines, and with the Declaration of Helsinki. This study was approved by the institutional review board of Hokkaido University Hospital (#022–0085). Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

A young patient diagnosed with advanced colon cancer and liver metastasis was found to have familial adenomatous polyposis (FAP) through comprehensive genomic analysis. Whole-genome array comparative genomic hybridization (aCGH) revealed germline deletions at chromosome 5q22.1-22.2 encompassing the entire APC gene. The patient and her son exhibited mild intellectual disability without developmental delay. This case highlights the need for further exploration of the characteristics associated with whole APC deletions. aCGH is a valuable tool for studying FAP and provides a detailed analysis of large deletions., (© 2024. The Author(s).)

High-risk neuroblastoma (HR-NB) patients remain far from obtaining optimal outcomes, with more than 50% relapse/regrowth rate despite current intensive multimodal therapy. This originated from the activation/proliferation of chemoresistant minimal residual disease (MRD). MRD with a significant prognostic was reported by several quantitative PCR (qPCR) or droplet digital PCR (ddPCR) assays quantitating different sets of NB-associated mRNAs (NB-mRNAs). The 7NB-mRNAs ddPCR assay quantitating CRMP1, DBH, DDC, GAP43, ISL1, PHOX2B, and TH mRNAs was reported to outperform other qPCR assays by a retrospective in-house observational study. In the present study, the Japan Children's Cancer Group (JCCG) Neuroblastoma Committee conducted a prospective multicenter observational study aimed at evaluating a prognostic value of MRD in bone marrow (BM-MRD) and peripheral blood (PB-MRD) detected by 7NB-mRNAs ddPCR assay. Between August 2018 and August 2022, 7 HR-NB patients who registered for JCCG clinical trials (JN-H-11 and JN-H-15) were enrolled. A total of 19 BM and 19 PB samples were collected, and 4/15 BM and 4/15 PB samples were classified as progressive disease (PD)/non-PD samples. BM-MRD and PB-MRD estimated area under curve (AUC) of 0.767 and 0.800 with a significant accuracy (AUC > 0.7). The present study validated a prognostic value of BM-MRD obtained by a previous study (AUC 0.723) and revealed the significant accuracy of PB-MRD as well as BM-MRD.

Background: Hereditary folate malabsorption-a rare disorder caused by impairment of the folate transporter-can develop into severe folate deficiency manifesting as megaloblastic anemia and occasionally thrombocytopenia. Reportedly, megaloblastic anemia can manifest with hemorrhagic episodes, possibly due to ineffective platelet production and platelet dysfunction. However, life-threatening hemorrhage events in hereditary folate malabsorption have not been well investigated., Case Presentation: A 3-month-old Japanese boy was transferred to our hospital due to thrombocytopenia and severe megaloblastic anemia. During a thorough examination of hematopoietic abnormalities, the patient suddenly went into cardiac arrest due to pulmonary hemorrhage. Although intravenous folate supplementation was started soon after the identification of folate deficiency, the patient died of circulatory defect and multiple organ failure. The cause of pulmonary hemorrhage, such as respiratory infection, could not be confirmed. Genetic investigation revealed a mutation in the SLC46A1 gene to be the cause of the hereditary folate malabsorption., Conclusion: We report an infantile case of hereditary folate malabsorption that progressed to lethal pulmonary hemorrhage before folate deficiency was identified. Clinicians should consider that megaloblastic anemia could lead to severe bleeding without warning, and that nutrient supplementation should be initiated as soon as possible., (© 2022. The Author(s).)

The Hokkaido medical personnel training plan connecting humans and medicine aims to train"Medical personnel for genome medicine"," Medical personnel for rare cancer and childhood cancer", and"Medical personnel who promote cancer measures according to patient's life stage". We have worked on preparing medical professionals who undergo training courses not only in the graduate school but also in the community medicine centers cooperating with central medical centers in Hokkaido. Furthermore, we have been committed to training medical staff who provide comprehensive healthcare for patients with cancer cross-regionally, cross-sectionally, and tumor-agnostically and researchers who can pursue genome medicine. The evaluation committee concluded that the plan was substantially advanced according to the evaluation guideline, and a committee member commented that the information through Web was assessable during the COVID-19 pandemic; in fact, it should be ensured by everyone. Based on these comments, we continuously work to develop human resources using content and information dissemination know-how accumulated in the Hokkaido medical personnel training plan.