PMID- 31452757
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200929
IS  - 1792-1074 (Print)
IS  - 1792-1082 (Electronic)
IS  - 1792-1074 (Linking)
VI  - 18
IP  - 3
DP  - 2019 Sep
TI  - Molecular mutation characteristics of mismatch and homologous recombination 
      repair genes in gastrointestinal cancer.
PG  - 2789-2798
LID - 10.3892/ol.2019.10607 [doi]
AB  - Gastrointestinal cancer is one of the most common types of cancer with high 
      mortality rates. Mutations in several genes are reportedly involved in the 
      progression of gastrointestinal cancer, including tumor protein 53 (TP53), APC 
      regulator of WNT signaling pathway (APC), KRAS proto-oncogene GTPase (KRAS) and 
      erb-b2 receptor tyrosine kinase 2 (ERBB2). Most notably, there are numerous 
      mutations in DNA repair genes, including mismatch repair (MMR) and homologous 
      recombination (HR) genes. The focus of the present study was to investigate the 
      effects of MMR and HR gene mutations on genomic instability in gastrointestinal 
      cancer. Using targeted capture and massively parallel genomic sequencing, 137 
      gastrointestinal cancer patients were analyzed for somatic single-nucleotide 
      variants (SNVs) and insertion-deletion (indel) mutations in the exon regions of 
      183 cancer driver genes, including 4 MMR genes [MutL homolog MLH1, MLH2, MLH6 and 
      PMS1 homolog 2, mismatch repair system component (PMS2)] and 15 HR genes [BRCA1 
      DNA repair associated (BRCA1), BRCA2 DNA repair associated (BRCA2), ATM 
      serine/threonine kinase (ATM), phosphatase and tensin homolog, BLM RecQ like 
      helicase, FA complementation group A, FA complementation group C, FA 
      complementation group D2, FA complementation group E, FA complementation group F, 
      FA complementation group G, nibrin, partner and localizer of BRCA2 and Werner 
      syndrome RecQ like helicase]. A number of frequently mutated genes, including but 
      not limited to, mechanistic target of rapamycin kinase, neurofibromin 1, APC and, 
      in particular, DNA repair genes, including PMS2, ATM and BRCA2, were identified. 
      Frequency analysis was performed based on the SNVs and indels in the 183 genes to 
      indirectly indicate the relative status of genomic instability in each patient. 
      Correlation analysis suggested that MMR and HR gene mutations directly affected 
      the count of SNVs and indels. Overall, 56 of the gastrointestinal cancer patients 
      (40%) were found to have an inactivation mutation (stopgain/frameshift/splicing) 
      in one or more of the four MMR genes, whereas 112 patients (82%) harbored at 
      least one HR gene inactivation mutation. In addition, patients with MMR or HR 
      inactivation variants had more SNVs and indels compared with patients with no 
      such mutations. No other clinical characteristics (including sex and age) 
      appeared to have a statistically significant impact. Further analysis indicated 
      that different MMR or HR genes exerted distinct effects on genomic instability. 
      The results obtained in the current study may lay a foundation for investigations 
      into the tumorigenic process and for the development of novel therapeutic 
      strategies for the treatment of gastrointestinal cancer.
FAU - Liu, Xingcun
AU  - Liu X
AD  - Department of Gastrointestinal Surgery, The First Affiliated Hospital of Anhui 
      Medical University, Hefei, Anhui 230601, P.R. China.
FAU - Yang, Haiping
AU  - Yang H
AD  - First Dimension Biosciences (Suzhou) Co., Ltd., Suzhou, Jiangsu 215126, P.R. 
      China.
FAU - Wu, Xiaohong
AU  - Wu X
AD  - First Dimension Biosciences (Suzhou) Co., Ltd., Suzhou, Jiangsu 215126, P.R. 
      China.
FAU - Huang, Kai
AU  - Huang K
AD  - Department of Gastrointestinal Surgery, The First Affiliated Hospital of Anhui 
      Medical University, Hefei, Anhui 230601, P.R. China.
FAU - Ma, Paul
AU  - Ma P
AD  - First Dimension Biosciences (Suzhou) Co., Ltd., Suzhou, Jiangsu 215126, P.R. 
      China.
FAU - Jiang, Pengpeng
AU  - Jiang P
AD  - Department of Gastrointestinal Surgery, The First Affiliated Hospital of Anhui 
      Medical University, Hefei, Anhui 230601, P.R. China.
FAU - Zheng, Weiqing
AU  - Zheng W
AD  - Department of Gastrointestinal Surgery, The First Affiliated Hospital of Anhui 
      Medical University, Hefei, Anhui 230601, P.R. China.
FAU - Tang, Tom
AU  - Tang T
AD  - First Dimension Biosciences (Suzhou) Co., Ltd., Suzhou, Jiangsu 215126, P.R. 
      China.
FAU - Liu, Dujuan
AU  - Liu D
AD  - First Dimension Biosciences (Suzhou) Co., Ltd., Suzhou, Jiangsu 215126, P.R. 
      China.
LA  - eng
PT  - Journal Article
DEP - 20190711
PL  - Greece
TA  - Oncol Lett
JT  - Oncology letters
JID - 101531236
PMC - PMC6676647
OTO - NOTNLM
OT  - gastrointestinal cancer
OT  - genomic instability
OT  - homologous recombination repair
OT  - inactivation mutation
OT  - mismatch repair
EDAT- 2019/08/28 06:00
MHDA- 2019/08/28 06:01
PMCR- 2019/07/11
CRDT- 2019/08/28 06:00
PHST- 2018/04/18 00:00 [received]
PHST- 2019/04/12 00:00 [accepted]
PHST- 2019/08/28 06:00 [entrez]
PHST- 2019/08/28 06:00 [pubmed]
PHST- 2019/08/28 06:01 [medline]
PHST- 2019/07/11 00:00 [pmc-release]
AID - OL-0-0-10607 [pii]
AID - 10.3892/ol.2019.10607 [doi]
PST - ppublish
SO  - Oncol Lett. 2019 Sep;18(3):2789-2798. doi: 10.3892/ol.2019.10607. Epub 2019 Jul 
      11.