Identification of novel mutations in endometrial cancer patients by whole-exome sequencing.
The aim of the present study was to identify genomic alterations in Taiwanese endometrial cancer patients. This information is vitally important in Taiwan, where endometrial cancer is the second most common gynecological cancer. We performed whole-exome sequencing on DNA from 14 tumor tissue samples from Taiwanese endometrial cancer patients. We used the Genome Analysis Tool kit software package for data analysis, and the dbSNP, Catalogue of Somatic Mutations in Cancer (COSMIC) and The Cancer Genome Atlas (TCGA) databases for comparisons. Variants were validated via Sanger sequencing. We identified 143 non-synonymous mutations in 756 canonical cancer-related genes and 1,271 non-synonymous mutations in non-canonical cancer-related genes in 14 endometrial samples. PTEN, KRAS and PIK3R1 were the most frequently mutated canonical cancer-related genes. Our results revealed nine potential driver genes (MAPT, IL24, MCM6, TSC1, BIRC2, CIITA, DST, CASP8 and NOTCH2) and 21 potential passenger genes (ARMCX4, IGSF10, VPS13C, DCT, DNAH14, TLN1, ZNF605, ZSCAN29, MOCOS, CMYA5, PCDH17, UGT1A8, CYFIP2, MACF1, NUDT5, JAKMIP1, PCDHGB4, FAM178A, SNX6, IMP4 and PCMTD1). The detected molecular aberrations led to putative activation of the mTOR, Wnt, MAPK, VEGF and ErbB pathways, as well as aberrant DNA repair, cell cycle control and apoptosis pathways. We characterized the mutational landscape and genetic alterations in multiple cellular pathways of endometrial cancer in the Taiwanese population.
Epigenome Research Center, China Medical University Hospital, Taichung 404, Taiwan, R.O.C.
Ya-Sian
YS
Chang
Department of Biological Science and Technology, National Chiao Tung University, Hsinchu 300, Taiwan, R.O.C.
Hsien-Da
HD
Huang
Department of Pathology, Changhua Christian Hospital, Changhua 500, Taiwan, R.O.C.
Kun-Tu
KT
Yeh
Epigenome Research Center, China Medical University Hospital, Taichung 404, Taiwan, R.O.C.
Jan-Gowth
JG
Chang
D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology; D059472:Exome / Q000235:genetics*; D005260:Female; D015894:Genome, Human; D023281:Genomics; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA
D009363:Neoplasm Proteins