Development and validation of next generation sequencing based 35-gene hereditary cancer panel

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

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Author(s)

  • Wing Chan
  • Mianne Lee
  • Zhen Xuan Yeo
  • Dingge Ying
  • Keith A. Grimaldi
  • Craig Pickering
  • Senthil K. Sundaram
  • Lawrence C. H. Tzang

Related Research Unit(s)

Detail(s)

Original languageEnglish
Article number9
Journal / PublicationHereditary Cancer in Clinical Practice
Volume18
Online published28 Apr 2020
Publication statusPublished - 2020

Link(s)

Abstract

Background: Understanding the genetic basis of cancer risk is a major international endeavor. The emergence of next-generation sequencing (NGS) in late 2000's has further accelerated the discovery of many cancer susceptibility genes. The use of targeted NGS-based multigene testing panels to provide comprehensive analysis of cancer susceptible genes has proven to be a viable option, with the accurate and robust detection of a wide range of clinically relevant variants in the targeted genes being crucial. Methods: We have developed and validated a targeted NGS-based test for hereditary cancer risk assessment using Illumina's NGS platform by analyzing the protein-coding regions of 35 hereditary cancer genes with a bioinformatics pipeline that utilizes standard practices in the field. This 35-gene hereditary cancer panel is designed to identify germline cancer-causing mutations for 8 different cancers: breast, ovarian, prostate, uterine, colorectal, pancreatic, stomach cancers and melanoma. The panel was validated using well-characterized DNA specimens [NIGMS Human Genetic Cell Repository], where DNA had been extracted using blood of individuals whose genetic variants had been previously characterized by the 1000 Genome Project and the Coriell Catalog. Results: The 35-gene hereditary cancer panel shows high sensitivity (99.9%) and specificity (100%) across 4820 variants including single nucleotide variants (SNVs) and small insertions and deletions (indel; up to 25 bp). The reproducibility and repeatability are 99.8 and 100%, respectively. Conclusions: The use of targeted NGS-based multigene testing panels to provide comprehensive analysis of cancer susceptible genes has been considered a viable option. In the present study, we developed and validated a 35-gene panel for testing 8 common cancers using next-generation sequencing (NGS). The performance of our hereditary cancer panel is assessed across a board range of variants in the 35 genes to support clinical use.

Research Area(s)

  • Hereditary cancer, Next generation sequencing, Multigene panel testing, Analytical validation, Genetic testing, OVARIAN-CANCER, BREAST, PREDISPOSITION, STANDARDS, VARIANTS, GENOMICS, GENES

Citation Format(s)

Development and validation of next generation sequencing based 35-gene hereditary cancer panel. / Chan, Wing; Lee, Mianne; Yeo, Zhen Xuan; Ying, Dingge; Grimaldi, Keith A.; Pickering, Craig; Yang, Michael M. S.; Sundaram, Senthil K.; Tzang, Lawrence C. H.

In: Hereditary Cancer in Clinical Practice, Vol. 18, 9, 2020.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

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