Abstract
BackgroundHigh 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.ResultsNine 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.ConclusionTP53 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.Electronic supplementary materialThe online version of this article (doi:10.1186/1756-0500-7-805) contains supplementary material, which is available to authorized users.
Highlights
High grade serous ovarian cancer is one of the poorly characterized malignancies
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) showed presence of alterations in only the cancer samples
Our results showed that TP53 alterations were present in all the tumors but not in the normal group
Summary
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. The generation sequencing (NGS) approach has become a powerful platform to complement clinical diagnosis and assist in therapeutic decision-making in cancer due to its improved sensitivity in mutation detection and fast-turnaround time compared to current gold standard methods. The Sanger sequencing method, introduced in 1970, has been the gold standard for mutation analysis in cancer diagnostics [2] It has a relatively low sensitivity, lower throughput with higher turnaround time and overall cost [3]. In comparison with the single gene analysis which is commonly done with the Sanger approach, the application of NGS in cancer diagnostics allows the analysis of multiple genes to identify druggable mutations and to generate a more complete genotype of the cancer
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