Objectives: Patients with germline mutations in mismatch repair genes (MLH1, MSH2, MSH6, PMS2) associated with Lynch syndrome (LS) have an increased lifetime risk of endometrial cancer (EC). Multi-gene panel testing (MGPT) is a recent hereditary cancer risk tool enabling next-generation sequencing of numerous genes in parallel. We determined the prevalence of actionable cancer predisposition gene mutations identified through MGPT in an EC patient cohort.
Methods: A single center retrospective cohort study was conducted of patients with EC who had a clinical indication for genetic testing and who underwent MGPT as part of standard of care treatment between 2012 and 2021. Pathogenic mutations were identified and actionable mutations were defined as those with clinical management implications. Additionally, the number of individuals identified with LS was compared between MGPT and tumor-based screening.
Results: The study included a total of 224 patients. Thirty-three patients [14.7%, 95% confidence interval (CI) = 10.4-20.1] had actionable mutations. Twenty-one patients (9.4%, 95% CI = 5.9-14.0) had mutations in LS genes (4 MLH1, 5 MSH2, 7 MSH6, 4 PMS2, 1 Epcam-MSH2). MGPT revealed two patients with LS (9.5% of LS cases) not identified through routine tumor-based screening. Thirteen patients (5.8%, 95% CI = 3.1-9.7) had at least one actionable mutation in a non-Lynch syndrome gene (6 CHEK2, 2 BRCA2, 2 ATM, 2 APC, 1 RAD51C, 1 BRCA1).
Conclusions: Germline MGPT is both feasible and informative as it identifies LS cases not found on tumor testing as well as additional actionable mutations in patients with EC.
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http://dx.doi.org/10.1016/j.ygyno.2022.04.003 | DOI Listing |
Brief Bioinform
November 2024
The Department of Medical Oncology, Jilin Cancer Hospital, No. 1066, Jinhu Road, Changchun, 130012, China.
Somatic variants play a crucial role in the occurrence and progression of cancer. However, in the absence of matched normal controls, distinguishing between germline and somatic variants becomes challenging in tumor samples. The existing tumor-only genomic analysis methods either suffer from limited performance or insufficient interpretability due to an excess of features.
View Article and Find Full Text PDFLung Cancer
December 2024
Department of Oncology, Centro Hospitalar Conde de Sao Januario, Estrada do Visconde de S. Januario, Macau, China. Electronic address:
Objective: Pulmonary sarcomatoid carcinoma (PSC) is a rare, heterogeneous subgroup of non-small cell lung cancer (NSCLC). Patients with advanced PSCs have poor survival due to resistance to chemotherapy and radiotherapy, and narrow access to targeted therapy. Immune checkpoint inhibitors (ICIs) offer new hope, whereas data on their effectiveness is limited.
View Article and Find Full Text PDFTher Adv Med Oncol
December 2024
Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre (PMCC), University Health Network (UHN), 700 University Avenue, 7-812, Toronto, ON M5G 2M9, Canada.
Background: Given advancements in adjuvant treatments for non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK)-targeted therapies, it is important to consider postoperative targeted therapies for other early-stage oncogene-addicted NSCLC. Exploring baseline outcomes for early-stage NSCLC with these rare mutations is crucial.
Objectives: This study aims to assess relapse-free survival (RFS) and overall survival (OS) in patients with resected early-stage NSCLC with rare targetable driver mutations.
Pancreatology
December 2024
Department of Internal Medicine, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea. Electronic address:
Background: Endoscopic ultrasound-guided tissue acquisition (EUS-TA) has become essential for diagnosing pancreatic ductal adenocarcinoma (PDAC) and is increasingly utilized for comprehensive genome profiling (CGP) to advance precision medicine. This systematic review and meta-analysis assess the feasibility and clinical utility of EUS-TA samples for CGP in PDAC.
Methods: We conducted a thorough systematic literature search in PubMed, EMBASE, and the Cochrane Library up to October 2023.
Crit Rev Oncol Hematol
December 2024
Pathology Unit, Department of Woman and Child's Health and Public Health Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy; Pathology Institute, Catholic University of Sacred Heart, 00168 Rome, Italy. Electronic address:
High-grade serous ovarian carcinoma (HGSOC) is the most aggressive subtype of epithelial ovarian cancer and a leading cause of mortality among gynecologic malignancies. This review aims to comprehensively analyze the morphological, immunohistochemical, and molecular features of HGSOC, highlighting its pathogenesis and identifying biomarkers with diagnostic, prognostic, and therapeutic significance. Special emphasis is placed on the role of tumor microenvironment (TME) and genomic instability in shaping the tumor's behavior and therapeutic vulnerabilities.
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