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A novel missense germline mutation in exon 2 of the hMSH2 gene in a HNPCC family from Southern Italy.
Cancer Lett. 2005 Jun 08; 223(2):285-91.CL

Abstract

Germline mutations within the mismatch repair (MMR) genes are generally found in colorectal cancer (CRC) patients with a positive family history for the presence of the neoplasia. Clinical standard criteria have been established to define hereditary-non-polyposis-colorectal cancer (HNPCC)-prone families. Interestingly, the number of MMR gene mutations found in kindreds not fulfilling these criteria is still increasing. In this work we report the identification of a novel germline mutation of the hMSH2 gene, in two CRC-bearing subjects. The two probands belong to a large kindred from South Italy with no history suggestive for cancer aggregation. On the other hand, the early-onset of the neoplasia as well as the presence of a high number of tumor infiltrating lymphocytes (TILs) in the histological specimens of both patients, prompted us to perform a comprehensive genetic analysis. This analysis included the evaluation of the microsatellite instability (MSI) status with five markers according to the National Cancer Institute recommendations, followed by direct sequencing of the hMLH1 and hMSH2 genes. Both probands were found to carry a germline missense (277 C>T) mutation leading to the change (L93F) of an amino acid residue in a highly conserved domain of the MSH2 protein. This mutation is accompanied by the loss of expression of the hMSH2 gene in the tumor tissue. Our findings suggest that in the presence of the above-mentioned criteria it may be useful to perform a molecular analysis of the MMR genes, even if the pedigree does not show marked aggregation of cancers.

Authors+Show Affiliations

Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi 'Magna Graecia' di Catanzaro, Campus di Germaneto, 88100 Catanzaro, Italy.No 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 availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

15896463

Citation

Baudi, Francesco, et al. "A Novel Missense Germline Mutation in Exon 2 of the hMSH2 Gene in a HNPCC Family From Southern Italy." Cancer Letters, vol. 223, no. 2, 2005, pp. 285-91.
Baudi F, Fersini G, Lavecchia A, et al. A novel missense germline mutation in exon 2 of the hMSH2 gene in a HNPCC family from Southern Italy. Cancer Lett. 2005;223(2):285-91.
Baudi, F., Fersini, G., Lavecchia, A., Terracciano, R., Leone, F., Quaresima, B., Faniello, M. C., De Paola, L., Doldo, P., Cuda, G., Costanzo, F., & Venuta, S. (2005). A novel missense germline mutation in exon 2 of the hMSH2 gene in a HNPCC family from Southern Italy. Cancer Letters, 223(2), 285-91.
Baudi F, et al. A Novel Missense Germline Mutation in Exon 2 of the hMSH2 Gene in a HNPCC Family From Southern Italy. Cancer Lett. 2005 Jun 8;223(2):285-91. PubMed PMID: 15896463.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A novel missense germline mutation in exon 2 of the hMSH2 gene in a HNPCC family from Southern Italy. AU - Baudi,Francesco, AU - Fersini,Giuseppina, AU - Lavecchia,Annamaria, AU - Terracciano,Rosa, AU - Leone,Francarlo, AU - Quaresima,Barbara, AU - Faniello,Maria C, AU - De Paola,Loredana, AU - Doldo,Patrizia, AU - Cuda,Giovanni, AU - Costanzo,Francesco, AU - Venuta,Salvatore, Y1 - 2004/11/25/ PY - 2004/08/06/received PY - 2004/09/26/revised PY - 2004/09/27/accepted PY - 2005/5/18/pubmed PY - 2005/7/22/medline PY - 2005/5/18/entrez SP - 285 EP - 91 JF - Cancer letters JO - Cancer Lett VL - 223 IS - 2 N2 - Germline mutations within the mismatch repair (MMR) genes are generally found in colorectal cancer (CRC) patients with a positive family history for the presence of the neoplasia. Clinical standard criteria have been established to define hereditary-non-polyposis-colorectal cancer (HNPCC)-prone families. Interestingly, the number of MMR gene mutations found in kindreds not fulfilling these criteria is still increasing. In this work we report the identification of a novel germline mutation of the hMSH2 gene, in two CRC-bearing subjects. The two probands belong to a large kindred from South Italy with no history suggestive for cancer aggregation. On the other hand, the early-onset of the neoplasia as well as the presence of a high number of tumor infiltrating lymphocytes (TILs) in the histological specimens of both patients, prompted us to perform a comprehensive genetic analysis. This analysis included the evaluation of the microsatellite instability (MSI) status with five markers according to the National Cancer Institute recommendations, followed by direct sequencing of the hMLH1 and hMSH2 genes. Both probands were found to carry a germline missense (277 C>T) mutation leading to the change (L93F) of an amino acid residue in a highly conserved domain of the MSH2 protein. This mutation is accompanied by the loss of expression of the hMSH2 gene in the tumor tissue. Our findings suggest that in the presence of the above-mentioned criteria it may be useful to perform a molecular analysis of the MMR genes, even if the pedigree does not show marked aggregation of cancers. SN - 0304-3835 UR - https://www.unboundmedicine.com/medline/citation/15896463/A_novel_missense_germline_mutation_in_exon_2_of_the_hMSH2_gene_in_a_HNPCC_family_from_Southern_Italy_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-3835(04)00768-2 DB - PRIME DP - Unbound Medicine ER -