Dataset Information

Utilization of multigene panels in hereditary cancer predisposition testing: analysis of more than 2,000 patients.

ABSTRACT:

Purpose

The aim of this study was to determine the clinical and molecular characteristics of 2,079 patients who underwent hereditary cancer multigene panel testing.

Methods

Panels included comprehensive analysis of 14-22 cancer susceptibility genes (BRCA1 and BRCA2 not included), depending on the panel ordered (BreastNext, OvaNext, ColoNext, or CancerNext). Next-generation sequencing and deletion/duplication analyses were performed for all genes except EPCAM (deletion/duplication analysis only). Clinical histories of ColoNext patients harboring mutations in genes with well-established diagnostic criteria were assessed to determine whether diagnostic/testing criteria were met.

Results

Positive rates were defined as the proportion of patients with a pathogenic mutation/likely pathogenic variant(s) and were as follows: 7.4% for BreastNext, 7.2% for OvaNext, 9.2% for ColoNext, and 9.6% for CancerNext. Inconclusive results were found in 19.8% of BreastNext, 25.6% of OvaNext, 15.1% of ColoNext, and 23.5% of CancerNext tests. Based on information submitted by clinicians, 30% of ColoNext patients with mutations in genes with well-established diagnostic criteria did not meet corresponding criteria.

Conclusion

Our data point to an important role for targeted multigene panels in diagnosing hereditary cancer predisposition, particularly for patients with clinical histories spanning several possible diagnoses and for patients with suspicious clinical histories not meeting diagnostic criteria for a specific hereditary cancer syndrome.

SUBMITTER: LaDuca H

PROVIDER: S-EPMC4225457 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Publications

Utilization of multigene panels in hereditary cancer predisposition testing: analysis of more than 2,000 patients.

LaDuca Holly H Stuenkel A J AJ Dolinsky Jill S JS Keiles Steven S Tandy Stephany S Pesaran Tina T Chen Elaine E Gau Chia-Ling CL Palmaer Erika E Shoaepour Kamelia K Shah Divya D Speare Virginia V Gandomi Stephanie S Chao Elizabeth E

Genetics in medicine : official journal of the American College of Medical Genetics 20140424 11

<h4>Purpose</h4>The aim of this study was to determine the clinical and molecular characteristics of 2,079 patients who underwent hereditary cancer multigene panel testing.<h4>Methods</h4>Panels included comprehensive analysis of 14-22 cancer susceptibility genes (BRCA1 and BRCA2 not included), depending on the panel ordered (BreastNext, OvaNext, ColoNext, or CancerNext). Next-generation sequencing and deletion/duplication analyses were performed for all genes except EPCAM (deletion/duplication ...[more]

PMID: 24763289

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Project description:Background: Breast cancer, the most prevalent malignancy in women worldwide, presents diverse onset patterns and genetic backgrounds. This study aims to examine the genetic landscape and clinical implications of rare mutations in Chinese breast cancer patients. Methods: Clinical data from 253 patients, including sporadic and familial cases, were analyzed. Comprehensive genomic profiling was performed, categorizing identified rare variants according to the American College of Medical Genetics (ACMG) guidelines. In silico protein modeling was used to analyze potentially pathogenic variants' impact on protein structure and function. Results: We detected 421 rare variants across patients. The most frequently mutated genes were ALK (22.2%), BARD1 (15.6%), and BRCA2 (15.0%). ACMG classification identified 7% of patients harboring Pathogenic/Likely Pathogenic (P/LP) variants, with one case displaying a pathogenic BRCA1 mutation linked to triple-negative breast cancer (TNBC). Also identified were two pathogenic MUTYH variants, previously associated with colon cancer but increasingly implicated in breast cancer. Variants of uncertain significance (VUS) were identified in 112 patients, with PTEN c.C804A showing the highest frequency. The role of these variants in sporadic breast cancer oncogenesis was suggested. In-depth exploration of previously unreported variants led to the identification of three potential pathogenic variants: ATM c.C8573T, MSH3 c.A2723T, and CDKN1C c.C221T. Their predicted impact on protein structure and stability suggests a functional role in cancer development. Conclusion: This study reveals a comprehensive overview of the genetic variants landscape in Chinese breast cancer patients, highlighting the prevalence and potential implications of rare variants. We emphasize the value of comprehensive genomic profiling in breast cancer management and the necessity of continuous research into understanding the functional impacts of these variants.

Dataset Information

Utilization of multigene panels in hereditary cancer predisposition testing: analysis of more than 2,000 patients.

Purpose

Methods

Results

Conclusion

Publications

Utilization of multigene panels in hereditary cancer predisposition testing: analysis of more than 2,000 patients.

Similar Datasets

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