Open AccessDetection of somatic BRCA 1/2 mutations in ovarian cancer – next‐generation sequencing analysis of 100 cases
Author(s) -
Koczkowska Magdalena,
Zuk Monika,
Gorczynski Adam,
Ratajska Magdalena,
Lewandowska Marzena,
Biernat Wojciech,
Limon Janusz,
Wasag Bartosz
Publication year - 2016
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.748
Subject(s) - sanger sequencing , germline , germline mutation , frameshift mutation , somatic cell , ovarian cancer , cold pcr , biology , cancer research , serous fluid , genetics , olaparib , mutation , cancer , dna sequencing , brca mutation , ovarian carcinoma , medicine , oncology , gene , point mutation , polymerase , poly adp ribose polymerase
The overall prevalence of germline BRCA 1/2 mutations is estimated between 11% and 15% of all ovarian cancers. Individuals with germline BRCA 1/2 alterations treated with the PARP 1 inhibitors ( iPARP 1) tend to respond better than patients with wild‐type BRCA 1/2. Additionally, also somatic BRCA 1/2 alterations induce the sensitivity to iPARP 1. Therefore, the detection of both germline and somatic BRCA 1/2 mutations is required for effective iPARP 1 treatment. The aim of this study was to identify the frequency and spectrum of germline and somatic BRCA 1/2 alterations in a group of Polish patients with ovarian serous carcinoma. In total, 100 formalin‐fixed paraffin‐embedded ( FFPE ) ovarian serous carcinoma tissues were enrolled to the study. Mutational analysis of BRCA 1 / 2 genes was performed by using next‐generation sequencing. The presence of pathogenic variants was confirmed by Sanger sequencing. In addition, to confirm the germline or somatic status of the mutation, the nonneoplastic tissue was analyzed by bidirectional Sanger sequencing. In total, 27 (28% of patient samples) mutations (20 in BRCA 1 and 7 in BRCA 2 ) were identified. For 22 of 27 patients, nonneoplastic cells were available and sequencing revealed the somatic character of two BRCA 1 (2/16; 12.5%) and two BRCA 2 (2/6; 33%) mutations. Notably, we identified six novel frameshift or nonsense BRCA 1/2 mutations. The heterogeneity of the detected mutations confirms the necessity of simultaneous analysis of BRCA 1 / 2 genes in all patients diagnosed with serous ovarian carcinoma. Moreover, the use of tumor tissue for mutational analysis allowed the detection of both somatic and germline BRCA 1/2 mutations.