Journal
CANCER MANAGEMENT AND RESEARCH
Volume 10, Issue -, Pages 3945-3954Publisher
DOVE MEDICAL PRESS LTD
DOI: 10.2147/CMAR.S172710
Keywords
gastric cancer; HER2; whole-genome sequencing; gene mutation; gene amplification
Categories
Funding
- National Science Foundation of China [81672327, 81802319, 81602411]
- Program of Shanghai Academic/Technology Research Leader [17XD1402600]
- Shanghai Municipal Education Commission - Gaofeng Clinical Medicine Grant Support [20161410]
- Development Grant for Clinical Trial [SHDC12017X06]
- Program for Outstanding Medical Academic Leader
Ask authors/readers for more resources
Objective: The aim of this study was to compare the molecular profiling, including somatic mutation and somatic copy number variation (SCNV), between human epidermal growth factor receptor 2 (HER2)-positive (HER2+) and HER2-negative (HER2-) gastric cancer patients. Patients and methods: Tumor samples were collected from 15 gastric cancer patients, including 10 HER2+ samples and five HER2- samples, which were diagnosed by immunohistochemistry. Whole-genome sequencing was performed by Illumina HiSeq PE150 instrument, along with somatic single nucleotide variant (SNV), somatic structural variation (SV) and SCNV analyses. Results: The average number of somatic SNVs and mutation spectrum were similar between HER2+ and HER2- samples. Transition of C>T was the main type of mutation. For somatic SV, number of intrachromosomal translocation (2,850.3 +/- 1,260.4 vs 1,157 +/- 586.6, P=0.015) and insertion of large fragment (1,125.6 +/- 457.4 vs 500 +/- 138.9, P=0.002) in HER2+ samples were higher than those in HER2- samples. For all samples, lysine methyltransferase 2C (KMT2C), ZNF91, TAF1 and MAP4 genes were identified as new significant mutated driver genes. KMT2C gene mutations were mainly detected in HER2+ samples (7/10), which were correlated with the lysine degradation pathway. SERF2 gene mutations were more common in HER2-samples (3/5) than in HER2+ samples (1/10). Copy number gain was the major type of SCNV in both groups, and the average number of SCNVs was similar. In the HER2+ samples, by using the GISTIC algorithm, amplification of known driver genes cyclin-dependent kinase 12 (CDK12, 6/10) and RARA (5/10) was mainly observed, and other amplifications including JUP, GJD3, KRT39, CDC6, RAPGEFL1, WIPF2, FAM65C, KLF5, DACH1 and PIBF1 genes were also observed. Amplifications of solute carrier family 12 member 7 (SLC12A7, 5/5), ITC40 (4/5) and GALNT9 (4/5) genes were mainly detected in HER2-samples. Conclusion: Differences in genomic landscape between HER2+ and HER2- gastric cancer samples were revealed in this study. KMT2C mutation and CDK12 amplification were mainly detected in HER2+ gastric cancer, whereas SERF2 mutation and SLC12A7 amplification were detected in HER2- gastric cancer.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available