Genetic alterations in endometrial cancer by targeted next-generation sequencing

Ya-Sian Chang; Hsien-Da Huang; Kun-Tu Yeh; Jan-Gowth Chang

doi:10.1016/j.yexmp.2015.11.026

Genetic alterations in endometrial cancer by targeted next-generation sequencing

Exp Mol Pathol. 2016 Feb;100(1):8-12. doi: 10.1016/j.yexmp.2015.11.026. Epub 2015 Nov 25.

Authors

Ya-Sian Chang¹, Hsien-Da Huang², Kun-Tu Yeh³, Jan-Gowth Chang⁴

Affiliations

¹ Epigenome Research Center, China Medical University Hospital, Taichung, Taiwan; Department of Laboratory Medicine, China Medical University Hospital, Taichung, Taiwan.
² Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan; Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu, Taiwan.
³ Department of Pathology, Changhua Christian Hospital, Changhua, Taiwan.
⁴ Epigenome Research Center, China Medical University Hospital, Taichung, Taiwan; Department of Laboratory Medicine, China Medical University Hospital, Taichung, Taiwan; School of Medicine, China Medical University, Taichung, Taiwan. Electronic address: d6781@mail.cmuh.org.tw.

PMID: 26626801
DOI: 10.1016/j.yexmp.2015.11.026

Abstract

Many genetic factors play important roles in the development of endometrial cancer. The aim of this study was to investigate genetic alterations in the Taiwanese population with endometrial cancer. DNA was extracted from 10 cases of fresh-frozen endometrial cancer tissue. The exomes of cancer-related genes were captured using the NimbleGen Comprehensive Cancer Panel (578 cancer-related genes) and sequenced using the Illumina Genomic Sequencing Platform. Our results revealed 120 variants in 99 genes, 21 of which were included in the Oncomine Cancer Research Panel used in the National Cancer Institute Match Trial. The 21 genes comprised 8 tumor suppressor candidates (ATM, MSH2, PIK3R1, PTCH1, PTEN, TET2, TP53, and TSC1) and 13 oncogene candidates (ALK, BCL9, CTNNB1, ERBB2, FGFR2, FLT3, HNF1A, KIT, MTOR, PDGFRA, PPP2R1A, PTPN11, and SF3B1). We identified a high frequency of mutations in PTEN (50%) and genes involved in the endometrial cancer-related molecular pathway, which involves the IL-7 signaling pathway (PIK3R1, n=1; AKT2, n=1; FOXO1, n=1). We report the mutational landscape of endometrial cancer in the Taiwanese population. We believe that this study will shed new light on fundamental aspects for understanding the molecular pathogenesis of endometrial cancer and may aid in the development of new targeted therapies.

Keywords: Endometrial cancer; IL-7 signaling pathway; Next-generation sequencing; PTEN mutation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Chromosome Mapping
Endometrial Neoplasms / genetics*
Endometrial Neoplasms / pathology
Exome / genetics
Female
Genetic Predisposition to Disease*
High-Throughput Nucleotide Sequencing / methods
Humans
Interleukin-7 / genetics
Interleukin-7 / metabolism
Mutation / genetics*
PTEN Phosphohydrolase / genetics*
Protein Tyrosine Phosphatase, Non-Receptor Type 11 / genetics
Receptor, ErbB-2 / genetics
Receptor, Fibroblast Growth Factor, Type 2 / genetics
Sequence Analysis, DNA / methods

Substances

Interleukin-7
ERBB2 protein, human
Receptor, ErbB-2
Receptor, Fibroblast Growth Factor, Type 2
PTPN11 protein, human
Protein Tyrosine Phosphatase, Non-Receptor Type 11
PTEN Phosphohydrolase
PTEN protein, human