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Novel germline hMSH2 genomic deletion and somatic hMSH2 mutations in a hereditary nonpolyposis colorectal cancer family.
Mutat Res. 2004 Apr 14; 548(1-2):19-25.MR

Abstract

Germline and somatic mutations of the hMSH2 gene were determined in a Japanese hereditary nonpolyposis colorectal cancer (HNPCC) family fulfilling the Amsterdam criteria. PCR-SSCP-sequencing of genomic DNA detected a somatic hMSH2 mutation of an A deletion at codon 227-229 in a duodenal carcinoma and a somatic hMSH2 mutation of an A insertion at codon 21 in a gastric carcinoma from affected family members, both carcinomas exhibiting high microsatellite instability. However, no germline hMSH2 mutation was detected by the PCR-SSCP-sequencing method. Genomic DNA was then analyzed by Southern blot hybridization using three hMSH2 cDNA probes (probe A involving exons 1-5, probe B involving exons 4-11 and probe C involving exons 9-16) after digestion by restriction enzymes, EcoRI, HindIII and NsiI. The NsiI digest of DNA from normal tissues of affected members exhibited an aberrant 8.6 kb restriction fragment, in addition to the normal 10.6 kb fragment, when hybridized to probes A and B. This suggested the presence of a heterozygous 2kb genomic deletion encompassing exon 4, 5 or 6. RT-PCR-sequencing revealed that the deleted region encompassed exon 5. This novel genomic deletion of the hMSH2 gene was confirmed to be pathogenic, and the Southern hybridization pattern was applied to the pre-symptomatic diagnosis.

Authors+Show Affiliations

Hereditary Tumor Research Project, Tokyo Metropolitan Komagome Hospital, and Institute of Molecular Oncology, Showa University, Tokyo, Japan. mmiyaki@opal.famille.ne.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

15063132

Citation

Miyaki, Michiko, et al. "Novel Germline hMSH2 Genomic Deletion and Somatic hMSH2 Mutations in a Hereditary Nonpolyposis Colorectal Cancer Family." Mutation Research, vol. 548, no. 1-2, 2004, pp. 19-25.
Miyaki M, Iijima T, Yamaguchi T, et al. Novel germline hMSH2 genomic deletion and somatic hMSH2 mutations in a hereditary nonpolyposis colorectal cancer family. Mutat Res. 2004;548(1-2):19-25.
Miyaki, M., Iijima, T., Yamaguchi, T., Shirahama, S., Ito, T., Yasuno, M., & Mori, T. (2004). Novel germline hMSH2 genomic deletion and somatic hMSH2 mutations in a hereditary nonpolyposis colorectal cancer family. Mutation Research, 548(1-2), 19-25.
Miyaki M, et al. Novel Germline hMSH2 Genomic Deletion and Somatic hMSH2 Mutations in a Hereditary Nonpolyposis Colorectal Cancer Family. Mutat Res. 2004 Apr 14;548(1-2):19-25. PubMed PMID: 15063132.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Novel germline hMSH2 genomic deletion and somatic hMSH2 mutations in a hereditary nonpolyposis colorectal cancer family. AU - Miyaki,Michiko, AU - Iijima,Takeru, AU - Yamaguchi,Tatsuro, AU - Shirahama,Shuya, AU - Ito,Taichi, AU - Yasuno,Masamichi, AU - Mori,Takeo, PY - 2003/09/11/received PY - 2003/12/01/revised PY - 2003/12/17/accepted PY - 2004/4/6/pubmed PY - 2004/5/21/medline PY - 2004/4/6/entrez SP - 19 EP - 25 JF - Mutation research JO - Mutat Res VL - 548 IS - 1-2 N2 - Germline and somatic mutations of the hMSH2 gene were determined in a Japanese hereditary nonpolyposis colorectal cancer (HNPCC) family fulfilling the Amsterdam criteria. PCR-SSCP-sequencing of genomic DNA detected a somatic hMSH2 mutation of an A deletion at codon 227-229 in a duodenal carcinoma and a somatic hMSH2 mutation of an A insertion at codon 21 in a gastric carcinoma from affected family members, both carcinomas exhibiting high microsatellite instability. However, no germline hMSH2 mutation was detected by the PCR-SSCP-sequencing method. Genomic DNA was then analyzed by Southern blot hybridization using three hMSH2 cDNA probes (probe A involving exons 1-5, probe B involving exons 4-11 and probe C involving exons 9-16) after digestion by restriction enzymes, EcoRI, HindIII and NsiI. The NsiI digest of DNA from normal tissues of affected members exhibited an aberrant 8.6 kb restriction fragment, in addition to the normal 10.6 kb fragment, when hybridized to probes A and B. This suggested the presence of a heterozygous 2kb genomic deletion encompassing exon 4, 5 or 6. RT-PCR-sequencing revealed that the deleted region encompassed exon 5. This novel genomic deletion of the hMSH2 gene was confirmed to be pathogenic, and the Southern hybridization pattern was applied to the pre-symptomatic diagnosis. SN - 0027-5107 UR - https://www.unboundmedicine.com/medline/citation/15063132/Novel_germline_hMSH2_genomic_deletion_and_somatic_hMSH2_mutations_in_a_hereditary_nonpolyposis_colorectal_cancer_family_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0027510703003257 DB - PRIME DP - Unbound Medicine ER -