Analysis and Comparison of Somatic Mutations in Paired Primary and Recurrent Epithelial Ovarian Cancer Samples

Abstract

The TP53 mutations have been proved to be predominated in ovarian cancer in a study from The Cancer Genome Atlas (TCGA). However, the molecular characteristics of recurrent ovarian cancers following initial treatment have been poorly estimated. This study was to investigate the pattern of somatic point mutations in matched paired samples of primary and recurrent epithelial ovarian cancers, using the OncoMap mutation detection protocol. We have adapted a high-throughput genotyping platform to determine the mutation status of a large panel of known cancer genes. OncoMap v.4.4 was used to evaluate genomic DNA isolated from a set of 92 formalin-fixed, paraffin-embedded (FFPE) tumors, consisting of matched paired samples of initially diagnosed and recurrent tumors from 46 epithelial ovarian cancer (EOC) patients. Mutations were observed in 33.7% of the samples, with 29.3% of these samples having a single mutation and the remaining 4.3% having two or more mutations. Among the 41 genes analyzed, 35 mutations were found in four genes, namely, CDKN2A (2.2%), KRAS (6.5%), MLH1 (8.2%) and TP53 (20.7%). TP53 was the most frequently mutated gene, but there was no correlation between the presence of mutation in any gene and clinical prognosis. Furthermore, somatic mutations did not differ between primary and recurrent ovarian carcinomas. Every mutation present in recurrent samples was detected in the corresponding primary sample. In conclusion, these OncoMap data of Korean EOC samples provide that somatic mutations were found in CDKN2A, KRAS, MLH1, and TP53. No differences in mutational status between primary and recurrent samples were detected. To understand the biology of tumor recurrence in epithelial ovarian cancer, more studies are necessary, including epigenetic modifications or additional mutations in other genes.

Primary tumor location predicts poor clinical outcome with cetuximab in RAS wild-type metastatic colorectal cancer

“…Mutational analysis was done using the SequenomMassARRAY technology platform (OncoMap version 4.0), as previously described [ 13 , 14 ]. A pathologist (JK) reviewed formalin-fixed paraffin-embedded tissue and marked tumor portions, where DNA was extracted from using the QIAamp DNA Tissue kit (Qiagen, Hilden, Germany) according to the manufacturer’s instructions.…”

Molecular Heterogeneity of Ewing Sarcoma as Detected by Ion Torrent Sequencing

“…V384D in MLH1 resulted from transversion mutation c.1151T>A. This mutation discovered in four ES patients, and the same mutation site was reported in epithelial ovarian cancer [ 16 ]. The A72V amino acid in PTPN11 induced by c.215C>T transition was found in one ES specimen.…”

Ovarian Cancers: Genetic Abnormalities, Tumor Heterogeneity and Progression, Clonal Evolution and Cancer Stem Cells

“…Few studies have explored the problem of the comparative analysis of the mutational spectrum of ovarian cancers in primary and recurrent tumors. A study performed by Kim and coworkers on 46 epithelial ovarian cancer patients showed that somatic mutations did not differ between primary and recurrent tumors: every mutation present in the recurrent samples was detected in the corresponding primary sample [ 24 ]. In another study, Castellarin and coworkers have investigated the genome mutations of primary, first and second relapse tumor cells (derived from ascites) of few ovarian cancer patients and have observed that 89% of mutations found in relapse tumors were present in matched primary tumors, thus indicating that relapsing HGS-OvCas arise from pre-existence and persistence of tumor clones, in association with the accumulation of relatively few new mutations [ 25 ].…”