Tags

Type your tag names separated by a space and hit enter

Detection of mismatch repair gene germline mutation carrier among Chinese population with colorectal cancer.
BMC Cancer. 2008 Feb 07; 8:44.BC

Abstract

BACKGROUND

Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant syndrome. The National Cancer Institute (NCI) has recommended the Revised Bethesda guidelines for screening HNPCC. There has been a great deal of research on the value of these tests in other countries. However, literature about the Chinese population is scarce. Our objective is to detect and study microsatellite instability (MSI) and mismatch repair (MMR) gene germline mutation carriers among a Chinese population with colorectal cancer.

METHODS

In 146 prospectively recruited consecutive patients with clinically proven colorectal cancer, MSI carriers were identified by analysis of tumor tissue using multiplex fluorescence polymerase chain reaction (PCR) using the NCI recommended panel and classified into microsatellite instability-low (MSI-L), microsatellite instability-high (MSI-H) and microsatellite stable (MSS) groups. Immunohistochemical staining for MSH2, MSH6 and MLH1 on tissue microarrays (TMAs) was performed, and methylation of the MLH1 promoter was analyzed by quantitative methylation specific PCR (MSP). Germline mutation analysis of blood samples was performed for MSH2, MSH6 and MLH1 genes.

RESULTS

Thirty-four out of the 146 colorectal cancers (CRCs, 23.2%) were MSI, including 19 MSI-H CRCs and 15 MSI-L CRCS. Negative staining for MSH2 was found in 8 CRCs, negative staining for MSH6 was found in 6 CRCs. One MSI-H CRC was negative for both MSH6 and MSH2. Seventeen CRCs stained negatively for MLH1. MLH1 promoter methylation was determined in 34 MSI CRCs. Hypermethylation of the MLH1 promoter occurred in 14 (73.7%) out of 19 MSI-H CRCs and 5 (33.3%) out of 15 MSI-L CRCs. Among the 34 MSI carriers and one MSS CRC with MLH1 negative staining, 8 had a MMR gene germline mutation, which accounted for 23.5% of all MSI colorectal cancers and 5.5% of all the colorectal cancers. Five patients harbored MSH2 germline mutations, and three patients harbored MSH6 germline mutations. None of the patients had an MLH1 mutation. Mutations were commonly located in exon 7 and 12 of MSH2 and exon 5 of MSH6. Right colonic lesions and mucinous carcinoma were not common in MSI carriers.

CONCLUSION

Our data may imply that the characteristics of HNPCC in the Chinese population are probably different from those of Western countries. Application of NCI recommended criteria may not be effective enough to identify Chinese HNPCC families. Further studies are necessary to echo or refute our results so as to make the NCI recommendation more universally applicable.

Authors+Show Affiliations

National Center of Colorectal Surgery, 3rd Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, 1 Jinling Road, Nanjing 210001, China. jinheiying@yahoo.com.cnNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

18257912

Citation

Jin, Hei-Ying, et al. "Detection of Mismatch Repair Gene Germline Mutation Carrier Among Chinese Population With Colorectal Cancer." BMC Cancer, vol. 8, 2008, p. 44.
Jin HY, Liu X, Li VK, et al. Detection of mismatch repair gene germline mutation carrier among Chinese population with colorectal cancer. BMC Cancer. 2008;8:44.
Jin, H. Y., Liu, X., Li, V. K., Ding, Y., Yang, B., Geng, J., Lai, R., Ding, S., Ni, M., & Zhao, R. (2008). Detection of mismatch repair gene germline mutation carrier among Chinese population with colorectal cancer. BMC Cancer, 8, 44. https://doi.org/10.1186/1471-2407-8-44
Jin HY, et al. Detection of Mismatch Repair Gene Germline Mutation Carrier Among Chinese Population With Colorectal Cancer. BMC Cancer. 2008 Feb 7;8:44. PubMed PMID: 18257912.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Detection of mismatch repair gene germline mutation carrier among Chinese population with colorectal cancer. AU - Jin,Hei-Ying, AU - Liu,Xiufang, AU - Li,Vicky Ka Ming, AU - Ding,Yijiang, AU - Yang,Bolin, AU - Geng,Jianxiang, AU - Lai,Rensheng, AU - Ding,Shuqing, AU - Ni,Min, AU - Zhao,Ronghua, Y1 - 2008/02/07/ PY - 2007/07/12/received PY - 2008/02/07/accepted PY - 2008/2/9/pubmed PY - 2008/5/21/medline PY - 2008/2/9/entrez SP - 44 EP - 44 JF - BMC cancer JO - BMC Cancer VL - 8 N2 - BACKGROUND: Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant syndrome. The National Cancer Institute (NCI) has recommended the Revised Bethesda guidelines for screening HNPCC. There has been a great deal of research on the value of these tests in other countries. However, literature about the Chinese population is scarce. Our objective is to detect and study microsatellite instability (MSI) and mismatch repair (MMR) gene germline mutation carriers among a Chinese population with colorectal cancer. METHODS: In 146 prospectively recruited consecutive patients with clinically proven colorectal cancer, MSI carriers were identified by analysis of tumor tissue using multiplex fluorescence polymerase chain reaction (PCR) using the NCI recommended panel and classified into microsatellite instability-low (MSI-L), microsatellite instability-high (MSI-H) and microsatellite stable (MSS) groups. Immunohistochemical staining for MSH2, MSH6 and MLH1 on tissue microarrays (TMAs) was performed, and methylation of the MLH1 promoter was analyzed by quantitative methylation specific PCR (MSP). Germline mutation analysis of blood samples was performed for MSH2, MSH6 and MLH1 genes. RESULTS: Thirty-four out of the 146 colorectal cancers (CRCs, 23.2%) were MSI, including 19 MSI-H CRCs and 15 MSI-L CRCS. Negative staining for MSH2 was found in 8 CRCs, negative staining for MSH6 was found in 6 CRCs. One MSI-H CRC was negative for both MSH6 and MSH2. Seventeen CRCs stained negatively for MLH1. MLH1 promoter methylation was determined in 34 MSI CRCs. Hypermethylation of the MLH1 promoter occurred in 14 (73.7%) out of 19 MSI-H CRCs and 5 (33.3%) out of 15 MSI-L CRCs. Among the 34 MSI carriers and one MSS CRC with MLH1 negative staining, 8 had a MMR gene germline mutation, which accounted for 23.5% of all MSI colorectal cancers and 5.5% of all the colorectal cancers. Five patients harbored MSH2 germline mutations, and three patients harbored MSH6 germline mutations. None of the patients had an MLH1 mutation. Mutations were commonly located in exon 7 and 12 of MSH2 and exon 5 of MSH6. Right colonic lesions and mucinous carcinoma were not common in MSI carriers. CONCLUSION: Our data may imply that the characteristics of HNPCC in the Chinese population are probably different from those of Western countries. Application of NCI recommended criteria may not be effective enough to identify Chinese HNPCC families. Further studies are necessary to echo or refute our results so as to make the NCI recommendation more universally applicable. SN - 1471-2407 UR - https://www.unboundmedicine.com/medline/citation/18257912/Detection_of_mismatch_repair_gene_germline_mutation_carrier_among_Chinese_population_with_colorectal_cancer_ L2 - https://bmccancer.biomedcentral.com/articles/10.1186/1471-2407-8-44 DB - PRIME DP - Unbound Medicine ER -