title: 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.
  
  
  CONCLUSIONS
  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.
authors.forename: Nurul-Syakima
authors.initials: NS
authors.lastname: Ab Mutalib
authors.forename: Saiful Effendi
authors.initials: SE
authors.lastname: Syafruddin
authors.forename: Reena Rahayu
authors.initials: RR
authors.lastname: Md Zain
authors.forename: Ahmad Zailani Hatta
authors.initials: AZ
authors.lastname: Mohd Dali
authors.forename: Ryia Illani
authors.initials: RI
authors.lastname: Mohd Yunos
authors.forename: Sazuita
authors.initials: S
authors.lastname: Saidin
authors.forename: Rahman
authors.initials: R
authors.lastname: Jamal
authors.affiliation: UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, 56000 Cheras, Kuala Lumpur, Malaysia. norfilza@ppukm.ukm.edu.my.
authors.forename: Norfilza M
authors.initials: NM
authors.lastname: Mokhtar
mesh_terms: D000077216:Carcinoma, Ovarian Epithelial; D018284:Cystadenocarcinoma, Serous / Q000453:epidemiology / Q000235:genetics*; D030541:Databases, Genetic; D005260:Female; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D060787:Neoplasm Grading; D009375:Neoplasms, Glandular and Epithelial / Q000453:epidemiology / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000453:epidemiology / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D016159:Tumor Suppressor Protein p53