PMID- 31729406
OWN - NLM
STAT- MEDLINE
DCOM- 20201112
LR  - 20221207
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 9
IP  - 1
DP  - 2019 Nov 15
TI  - Somatic mutation profiling and HER2 status in KRAS-positive Chinese colorectal 
      cancer patients.
PG  - 16894
LID - 10.1038/s41598-019-53039-y [doi]
LID - 16894
AB  - KRAS is an independent negative predictor for anti-epidermal growth factor 
      receptor (anti-EGFR) treatment in colorectal cancers (CRCs). However, 30% to 50% 
      of CRC patients are KRAS-positive and do not benefit from anti-EGFR therapy. In 
      this study, we investigated the mutational features and clinical significance of 
      KRAS-positive Chinese CRC patients. A total of 139 Chinese CRC patients who 
      received clinical KRAS testing (Sanger sequencing) were examined by 
      immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Fifty 
      KRAS-positive specimens were further detected by next-generation sequencing 
      (NGS). The most prevalent mutation in KRAS was G12D (46%), followed by G12V 
      (20%), and G13D (18%). In addition to KRAS, 72 unique alterations in another 12 
      genes were also detected. The most common mutated genes were TP53 (62%), APC 
      (46%), and PIK3CA (22%). The proportion of HER2 amplifications in KRAS-positive 
      CRC patients was 4.4%, which was lower than that in KRAS -negative CRC patients 
      (14.3%). No relationship was found between HER2 amplification and KRAS status 
      (p = 0.052). However, the odds ratio is very low (0.279). In addition, these gene 
      mutations were not significantly associated with age, sex, tumor size, lymph node 
      metastasis, mismatch repair-deficient, or tumor differentiation. However, TP53 
      mutations were more prevalent in colon cancer with KRAS mutations than in rectal 
      cancer (75.0% vs 28.6%, respectively, p = 0.004). The negative predictive value 
      of the IHC analysis for predicting HER2 amplification reached to 98.39%, while 
      the positive predictive value reached only 50%. Overall, the mutation profiling 
      of Chinese CRC patients with KRAS mutations is different from that of Western CRC 
      patients. Our results will help us to understand the molecular features of 
      Chinese CRC patients.
FAU - Dong, Zhouhuan
AU  - Dong Z
AD  - Chinese PLA General Hospital, Department of Pathology, Beijing, 100853, China.
FAU - Kong, Linghong
AU  - Kong L
AD  - ChuiYangLiu Hospital affiliated to Tsinghua University, Department of Pathology, 
      Beijing, 100022, China.
FAU - Wan, Zhiyi
AU  - Wan Z
AD  - ChuiYangLiu Hospital affiliated to Tsinghua University, Department of Pathology, 
      Beijing, 100022, China.
FAU - Zhu, Fengwei
AU  - Zhu F
AD  - Chinese PLA General Hospital, Department of Pathology, Beijing, 100853, China.
FAU - Zhong, Mei
AU  - Zhong M
AD  - Chinese PLA General Hospital, Department of Pathology, Beijing, 100853, China.
FAU - Lv, Yali
AU  - Lv Y
AD  - Chinese PLA General Hospital, Department of Pathology, Beijing, 100853, China.
FAU - Zhao, Po
AU  - Zhao P
AD  - Chinese PLA General Hospital, Department of Pathology, Beijing, 100853, China.
FAU - Shi, Huaiyin
AU  - Shi H
AD  - Chinese PLA General Hospital, Department of Pathology, Beijing, 100853, China. 
      shihuaiyin@sina.com.
LA  - eng
PT  - Journal Article
DEP - 20191115
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (KRAS protein, human)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
SB  - IM
MH  - Adenocarcinoma/epidemiology/ethnology/*genetics
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Amino Acid Substitution
MH  - Asian People/genetics/statistics & numerical data
MH  - China/epidemiology
MH  - Cohort Studies
MH  - Colorectal Neoplasms/epidemiology/ethnology/*genetics
MH  - DNA Mutational Analysis/*methods
MH  - Female
MH  - Gene Amplification
MH  - Gene Frequency
MH  - High-Throughput Nucleotide Sequencing
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Point Mutation
MH  - Proto-Oncogene Proteins p21(ras)/*genetics
MH  - Receptor, ErbB-2/*genetics
PMC - PMC6858340
COIS- The authors declare no competing interests.
EDAT- 2019/11/16 06:00
MHDA- 2020/11/13 06:00
PMCR- 2019/11/15
CRDT- 2019/11/16 06:00
PHST- 2019/01/30 00:00 [received]
PHST- 2019/10/21 00:00 [accepted]
PHST- 2019/11/16 06:00 [entrez]
PHST- 2019/11/16 06:00 [pubmed]
PHST- 2020/11/13 06:00 [medline]
PHST- 2019/11/15 00:00 [pmc-release]
AID - 10.1038/s41598-019-53039-y [pii]
AID - 53039 [pii]
AID - 10.1038/s41598-019-53039-y [doi]
PST - epublish
SO  - Sci Rep. 2019 Nov 15;9(1):16894. doi: 10.1038/s41598-019-53039-y.