A BEGINNING SURVEY OF BRCA1 AND BRCA2 MUTATIONS AMONG VIETNAMESE OVARIAN CARCINOMAS POPULATION BY ION PERSONAL GENOME MACHINE PLATFORMS

Abstract

BRCA1 and BRCA2 are two important tumor suppressor genes, gemline and somatic mutations of these two genes in ovarian carcinomas are sensitive for treatment with ADP-ribose polymerase enzyme inhibitor (PARPi). Recently, several PARPi drugs, such as Olaparib and Rucaparib, were approved for ovarian cancer with BRCA1/2 germline mutations by Food and Drug Administration (FDA), and for both germline and somatic mutations by European Medicines Agency (EMA). However, there is no reliable data currently about prevalence of mutations of these two genes in ovarian carcinomas population for treatment. Therefore, we conducted the survey of prevalence of the BRCA1/2 germline and somatic mutations among ovarian carcinomas patients in Vietnamese population. In this study, we sequenced these two genes using Ion Torrent PGM. Subjects of the study were 11 formalin-fixed, paraffin-embedded tumor (FFPE) samples from 11 patients with ovarian carcinomas obtained from Tu Du Hospital of Obstetrics and Gynecology. DNA from each tumor sample was pretreated uracil-DNA glycosylase to eliminate artifacts causing by cytosine deamination. Mutiplex PCR then was performed on the DNA samples and two positive controls containing known mutations by using Oncomine BRCA Research Assay. Of the sequenced 11 samples, a pathogenic mutation (9.1%) detected in BRCA1 gene was a nonsense point mutation causing stop codon at the position of amino acid 1772. Consequently, our workflow showed sensitivity and specificity for screening BRCA1/2 mutation with FFPE tumor samples.