Detection of germline mutations in patients with epithelial ovarian cancer using multi-gene panels: Beyond BRCA1/2

Kyung Jin Eoh, Ji Eun Kim, Hyung Seok Park, Seung Tae Lee, Ji Soo Park, Jung Woo Han, Jung Yun Lee, Sunghoon Kim, Sang Wun Kim, Jae-Hoon Kim, YoungTae Kim, Eun Ji Nam

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Purpose Next-generation sequencing (NGS) allows simultaneous sequencing of multiple cancer susceptibility genes and may represent a more efficient and less expensive approach than sequential testing. We assessed the frequency of germline mutations in individuals with epithelial ovarian cancer (EOC), using multi-gene panels and NGS. Materials and Methods Patients with EOC (n=117) with/without a family history of breast or ovarian cancer were recruited consecutively, from March 2016 to December 2016. Germline DNA was sequenced using 35-gene NGS panel, in order to identify mutations. Upon the detection of a genetic alteration using the panel, results were cross-validated using direct sequencing. Results Thirty-eight patients (32.5%) had 39 pathogenic or likely pathogenic mutations in eight genes, including BRCA1 (n=21), BRCA2 (n=10), BRIP1 (n=1), CHEK2 (n=2), MSH2 (n=1), POLE (n=1), RAD51C (n=2), and RAD51D (n=2). Among 64 patients with a family history of cancer, 27 (42.2%) had 27 pathogenic or likely pathogenic mutations, and six (9.3%) had mutations in genes other than BRCA1/2, such as CHECK2, MSH2, POLE, and RAD51C. Fifty-five patients (47.0%) were identified to carry only variants of uncertain significance. Conclusion Using the multi-gene panel test, we found that, of all patients included in our study, 32.5% had germline cancer-predisposing mutations. NGS was confirmed to substantially improve the detection rates of a wide spectrum of mutations in EOC patients compared with those obtained with the BRCA1/2 testing alone.

Original languageEnglish
Pages (from-to)917-925
Number of pages9
JournalCancer Research and Treatment
Volume50
Issue number3
DOIs
Publication statusPublished - 2018 Jul 1

Fingerprint

Germ-Line Mutation
Mutation
BRCA1 Gene
Genes
Neoplasm Genes
Ovarian Neoplasms
Ovarian epithelial cancer
Neoplasms
Breast Neoplasms
DNA

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Eoh, Kyung Jin ; Kim, Ji Eun ; Park, Hyung Seok ; Lee, Seung Tae ; Park, Ji Soo ; Han, Jung Woo ; Lee, Jung Yun ; Kim, Sunghoon ; Kim, Sang Wun ; Kim, Jae-Hoon ; Kim, YoungTae ; Nam, Eun Ji. / Detection of germline mutations in patients with epithelial ovarian cancer using multi-gene panels : Beyond BRCA1/2. In: Cancer Research and Treatment. 2018 ; Vol. 50, No. 3. pp. 917-925.
@article{4a965fceb5a24129932174e3afbf2396,
title = "Detection of germline mutations in patients with epithelial ovarian cancer using multi-gene panels: Beyond BRCA1/2",
abstract = "Purpose Next-generation sequencing (NGS) allows simultaneous sequencing of multiple cancer susceptibility genes and may represent a more efficient and less expensive approach than sequential testing. We assessed the frequency of germline mutations in individuals with epithelial ovarian cancer (EOC), using multi-gene panels and NGS. Materials and Methods Patients with EOC (n=117) with/without a family history of breast or ovarian cancer were recruited consecutively, from March 2016 to December 2016. Germline DNA was sequenced using 35-gene NGS panel, in order to identify mutations. Upon the detection of a genetic alteration using the panel, results were cross-validated using direct sequencing. Results Thirty-eight patients (32.5{\%}) had 39 pathogenic or likely pathogenic mutations in eight genes, including BRCA1 (n=21), BRCA2 (n=10), BRIP1 (n=1), CHEK2 (n=2), MSH2 (n=1), POLE (n=1), RAD51C (n=2), and RAD51D (n=2). Among 64 patients with a family history of cancer, 27 (42.2{\%}) had 27 pathogenic or likely pathogenic mutations, and six (9.3{\%}) had mutations in genes other than BRCA1/2, such as CHECK2, MSH2, POLE, and RAD51C. Fifty-five patients (47.0{\%}) were identified to carry only variants of uncertain significance. Conclusion Using the multi-gene panel test, we found that, of all patients included in our study, 32.5{\%} had germline cancer-predisposing mutations. NGS was confirmed to substantially improve the detection rates of a wide spectrum of mutations in EOC patients compared with those obtained with the BRCA1/2 testing alone.",
author = "Eoh, {Kyung Jin} and Kim, {Ji Eun} and Park, {Hyung Seok} and Lee, {Seung Tae} and Park, {Ji Soo} and Han, {Jung Woo} and Lee, {Jung Yun} and Sunghoon Kim and Kim, {Sang Wun} and Jae-Hoon Kim and YoungTae Kim and Nam, {Eun Ji}",
year = "2018",
month = "7",
day = "1",
doi = "10.4143/crt.2017.220",
language = "English",
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Eoh, KJ, Kim, JE, Park, HS, Lee, ST, Park, JS, Han, JW, Lee, JY, Kim, S, Kim, SW, Kim, J-H, Kim, Y & Nam, EJ 2018, 'Detection of germline mutations in patients with epithelial ovarian cancer using multi-gene panels: Beyond BRCA1/2', Cancer Research and Treatment, vol. 50, no. 3, pp. 917-925. https://doi.org/10.4143/crt.2017.220

Detection of germline mutations in patients with epithelial ovarian cancer using multi-gene panels : Beyond BRCA1/2. / Eoh, Kyung Jin; Kim, Ji Eun; Park, Hyung Seok; Lee, Seung Tae; Park, Ji Soo; Han, Jung Woo; Lee, Jung Yun; Kim, Sunghoon; Kim, Sang Wun; Kim, Jae-Hoon; Kim, YoungTae; Nam, Eun Ji.

In: Cancer Research and Treatment, Vol. 50, No. 3, 01.07.2018, p. 917-925.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Detection of germline mutations in patients with epithelial ovarian cancer using multi-gene panels

T2 - Beyond BRCA1/2

AU - Eoh, Kyung Jin

AU - Kim, Ji Eun

AU - Park, Hyung Seok

AU - Lee, Seung Tae

AU - Park, Ji Soo

AU - Han, Jung Woo

AU - Lee, Jung Yun

AU - Kim, Sunghoon

AU - Kim, Sang Wun

AU - Kim, Jae-Hoon

AU - Kim, YoungTae

AU - Nam, Eun Ji

PY - 2018/7/1

Y1 - 2018/7/1

N2 - Purpose Next-generation sequencing (NGS) allows simultaneous sequencing of multiple cancer susceptibility genes and may represent a more efficient and less expensive approach than sequential testing. We assessed the frequency of germline mutations in individuals with epithelial ovarian cancer (EOC), using multi-gene panels and NGS. Materials and Methods Patients with EOC (n=117) with/without a family history of breast or ovarian cancer were recruited consecutively, from March 2016 to December 2016. Germline DNA was sequenced using 35-gene NGS panel, in order to identify mutations. Upon the detection of a genetic alteration using the panel, results were cross-validated using direct sequencing. Results Thirty-eight patients (32.5%) had 39 pathogenic or likely pathogenic mutations in eight genes, including BRCA1 (n=21), BRCA2 (n=10), BRIP1 (n=1), CHEK2 (n=2), MSH2 (n=1), POLE (n=1), RAD51C (n=2), and RAD51D (n=2). Among 64 patients with a family history of cancer, 27 (42.2%) had 27 pathogenic or likely pathogenic mutations, and six (9.3%) had mutations in genes other than BRCA1/2, such as CHECK2, MSH2, POLE, and RAD51C. Fifty-five patients (47.0%) were identified to carry only variants of uncertain significance. Conclusion Using the multi-gene panel test, we found that, of all patients included in our study, 32.5% had germline cancer-predisposing mutations. NGS was confirmed to substantially improve the detection rates of a wide spectrum of mutations in EOC patients compared with those obtained with the BRCA1/2 testing alone.

AB - Purpose Next-generation sequencing (NGS) allows simultaneous sequencing of multiple cancer susceptibility genes and may represent a more efficient and less expensive approach than sequential testing. We assessed the frequency of germline mutations in individuals with epithelial ovarian cancer (EOC), using multi-gene panels and NGS. Materials and Methods Patients with EOC (n=117) with/without a family history of breast or ovarian cancer were recruited consecutively, from March 2016 to December 2016. Germline DNA was sequenced using 35-gene NGS panel, in order to identify mutations. Upon the detection of a genetic alteration using the panel, results were cross-validated using direct sequencing. Results Thirty-eight patients (32.5%) had 39 pathogenic or likely pathogenic mutations in eight genes, including BRCA1 (n=21), BRCA2 (n=10), BRIP1 (n=1), CHEK2 (n=2), MSH2 (n=1), POLE (n=1), RAD51C (n=2), and RAD51D (n=2). Among 64 patients with a family history of cancer, 27 (42.2%) had 27 pathogenic or likely pathogenic mutations, and six (9.3%) had mutations in genes other than BRCA1/2, such as CHECK2, MSH2, POLE, and RAD51C. Fifty-five patients (47.0%) were identified to carry only variants of uncertain significance. Conclusion Using the multi-gene panel test, we found that, of all patients included in our study, 32.5% had germline cancer-predisposing mutations. NGS was confirmed to substantially improve the detection rates of a wide spectrum of mutations in EOC patients compared with those obtained with the BRCA1/2 testing alone.

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U2 - 10.4143/crt.2017.220

DO - 10.4143/crt.2017.220

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AN - SCOPUS:85049799886

VL - 50

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