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Molecular characterization of serous ovarian carcinoma using a multigene next generation sequencing cancer panel approach.

ABSTRACT: BACKGROUND:High grade serous ovarian cancer is one of the poorly characterized malignancies. This study aimed to elucidate the mutational events in Malaysian patients with high grade serous ovarian cancer by performing targeted sequencing on 50 cancer hotspot genes. RESULTS:Nine high grade serous ovarian carcinoma samples and ten normal ovarian tissues were obtained from Universiti Kebangsaan Malaysia Medical Center (UKMMC) and the Kajang Hospital. The Ion AmpliSeq™ Cancer Hotspot Panel v2 targeting "mutation-hotspot region" in 50 most common cancer-associated genes was utilized. A total of 20 variants were identified in 12 genes. Eleven (55%) were silent alterations and nine (45%) were missense mutations. Six of the nine missense mutations were predicted to be deleterious while the other three have low or neutral protein impact. Eight genes were altered in both the tumor and normal groups (APC, EGFR, FGFR3, KDR, MET, PDGFRA, RET and SMO) while four genes (TP53, PIK3CA, STK11 and KIT) were exclusively altered in the tumor group. TP53 alterations were present in all the tumors but not in the normal group. Six deleterious mutations in TP53 (p.R175H, p.H193R, p.Y220C, p.Y163C, p.R282G and p.Y234H) were identified in eight serous ovarian carcinoma samples and none in the normal group. CONCLUSION:TP53 remains as the most frequently altered gene in high grade serous ovarian cancer and Ion Torrent Personal Genome Machine (PGM) in combination with Ion Ampliseq™ Cancer Hotspot Panel v2 were proven to be instrumental in identifying a wide range of genetic alterations simultaneously from a minute amount of DNA. However, larger series of validation targeting more genes are necessary in order to shed a light on the molecular events underlying pathogenesis of this cancer.

SUBMITTER: Ab Mutalib NS

PROVIDER: S-EPMC4242548 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Molecular characterization of serous ovarian carcinoma using a multigene next generation sequencing cancer panel approach.

Ab Mutalib Nurul-Syakima NS Syafruddin Saiful Effendi SE Md Zain Reena Rahayu RR Mohd Dali Ahmad Zailani Hatta AZ Mohd Yunos Ryia Illani RI Saidin Sazuita S Jamal Rahman R Mokhtar Norfilza M NM

BMC research notes 20141117

<h4>Background</h4>High grade serous ovarian cancer is one of the poorly characterized malignancies. This study aimed to elucidate the mutational events in Malaysian patients with high grade serous ovarian cancer by performing targeted sequencing on 50 cancer hotspot genes.<h4>Results</h4>Nine high grade serous ovarian carcinoma samples and ten normal ovarian tissues were obtained from Universiti Kebangsaan Malaysia Medical Center (UKMMC) and the Kajang Hospital. The Ion AmpliSeq™ Cancer Hotspot ...[more]

PMID: 25404506

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Project description:Germline variants in BRCA1 and BRCA2 (BRCA1/2) genes are the most common cause of hereditary breast cancer. However, a significant number of cases are not linked to these two genes and additional high-, moderate- and low-penetrance genes have been identified in breast cancer. The advent of next-generation sequencing (NGS) allowed simultaneous sequencing of multiple cancer-susceptibility genes and prompted research in this field. So far, cancer-predisposition genes other than BRCA1/2 have not been studied in the population of Bahrain. We performed a targeted NGS using a multi-panel covering 180 genes associated with cancer predisposition to investigate the spectrum and frequency of germline variants in 54 women with a positive personal and/or family history of breast cancer. Sequencing analysis revealed germline variants in 29 (53.7%) patients. Five pathogenic/likely pathogenic variants in four DNA repair pathway-related genes were identified in five unrelated patients (9.3%). Two BRCA1 variants, namely the missense variant c.287A>G (p.Asp96Gly) and the truncating variant c.1066C>T (p.Gln356Ter), were detected in two patients (3.7%). Three variants in non-BRCA1/2 genes were detected in three patients (1.85% each) with a strong family history of breast cancer. These included a monoallelic missense variant c.1187G>A (p.Gly396Asp) in MUTYH gene, and two truncating variants namely c.3343C>T (p.Arg1115Ter) in MLH3 gene and c.1826G>A (p.Trp609Ter) in PMS1 gene. Other variants of uncertain significance (VUS) were also detected, and some of them were found together with the deleterious variants. In this first application of NGS-based multigene testing in Bahraini women with breast cancer, we show that multigene testing can yield additional genomic information on low-penetrance genes, although the clinical significance of these genes has not been fully appreciated yet. Our findings also provide valuable epidemiological information for future studies and highlight the importance of genetic testing, and an NGS-based multigene analysis may be applied supplementary to traditional genetic counseling.

Dataset Information

Molecular characterization of serous ovarian carcinoma using a multigene next generation sequencing cancer panel approach.

Publications

Molecular characterization of serous ovarian carcinoma using a multigene next generation sequencing cancer panel approach.

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