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, Young Tae Kim, Eun Ji Nam

Research output: Contribution to journalArticle

9 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, Young Tae ; 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 Kim, {Jae Hoon} and Kim, {Young Tae} and Nam, {Eun Ji}",
year = "2018",
month = "7",
day = "1",
doi = "10.4143/crt.2017.220",
language = "English",
volume = "50",
pages = "917--925",
journal = "Cancer Research and Treatment",
issn = "1598-2998",
publisher = "Korean Cancer Association",
number = "3",

}

Eoh, KJ, Kim, JE, Park, HS, Lee, ST, Park, JS, Han, JW, Lee, JY, Kim, S, Kim, SW, Kim, JH, Kim, YT & 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, Young Tae; 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, Young Tae

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.

UR - http://www.scopus.com/inward/record.url?scp=85049799886&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85049799886&partnerID=8YFLogxK

U2 - 10.4143/crt.2017.220

DO - 10.4143/crt.2017.220

M3 - Article

C2 - 29020732

AN - SCOPUS:85049799886

VL - 50

SP - 917

EP - 925

JO - Cancer Research and Treatment

JF - Cancer Research and Treatment

SN - 1598-2998

IS - 3

ER -