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The importance of functional testing in the genetic assessment of Muir-Torre syndrome, a clinical subphenotype of HNPCC.
Int J Oncol. 2006 Jan; 28(1):149-53.IJ

Abstract

A majority of families with hereditary nonpolyposis colorectal cancer (HNPCC) are attributable to germline mutations in three DNA mismatch repair (MMR) genes, MLH1, MSH2 and MSH6. However, the clinical phenotype appears to reflect a complex interplay between the predisposing mutation and putative constitutional and somatic modifiers. Certain MMR gene mutations predispose to combined occurrence of cutaneous sebaceous gland neoplasms and visceral malignancies, which is known as Muir-Torre syndrome (MTS) and regarded as a phenotypic variant of HNPCC. The sebaceous tumors associated with MTS appear in many patients before visceral malignancies providing important predictability of HNPCC-related integral cancers in mutation carriers. Since most sebaceous skin tumors are, however, sporadic, the contribution of non-truncating mutations found in skin cancer patients is difficult to interpret and genetic assessment of MTS requires a functional test. Here, we studied the repair efficiency of the two MSH2 missense mutations, L187P and C697F, found in HNPCC families including a few mutation carriers with sebaceous skin tumors. Both mutations were completely deficient in an MMR assay, which together with tumor findings suggested their predisposing role in both internal and skin malignancies in the families.

Authors+Show Affiliations

Department of Biological and Environmental Sciences, Genetics, University of Helsinki, Helsinki, Finland.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 availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

16327991

Citation

Ollila, Saara, et al. "The Importance of Functional Testing in the Genetic Assessment of Muir-Torre Syndrome, a Clinical Subphenotype of HNPCC." International Journal of Oncology, vol. 28, no. 1, 2006, pp. 149-53.
Ollila S, Fitzpatrick R, Sarantaus L, et al. The importance of functional testing in the genetic assessment of Muir-Torre syndrome, a clinical subphenotype of HNPCC. Int J Oncol. 2006;28(1):149-53.
Ollila, S., Fitzpatrick, R., Sarantaus, L., Kariola, R., Ambus, I., Velsher, L., Hsieh, E., Andersen, M. K., Raevaara, T. E., Gerdes, A. M., Mangold, E., Peltomäki, P., Lynch, H. T., & Nyström, M. (2006). The importance of functional testing in the genetic assessment of Muir-Torre syndrome, a clinical subphenotype of HNPCC. International Journal of Oncology, 28(1), 149-53.
Ollila S, et al. The Importance of Functional Testing in the Genetic Assessment of Muir-Torre Syndrome, a Clinical Subphenotype of HNPCC. Int J Oncol. 2006;28(1):149-53. PubMed PMID: 16327991.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The importance of functional testing in the genetic assessment of Muir-Torre syndrome, a clinical subphenotype of HNPCC. AU - Ollila,Saara, AU - Fitzpatrick,Roslyn, AU - Sarantaus,Laura, AU - Kariola,Reetta, AU - Ambus,Ingrid, AU - Velsher,Lea, AU - Hsieh,Eugene, AU - Andersen,Mette Klarskov, AU - Raevaara,Tiina E, AU - Gerdes,Anne-Marie, AU - Mangold,Elisabeth, AU - Peltomäki,Päivi, AU - Lynch,Henry T, AU - Nyström,Minna, PY - 2005/12/6/pubmed PY - 2006/1/26/medline PY - 2005/12/6/entrez SP - 149 EP - 53 JF - International journal of oncology JO - Int J Oncol VL - 28 IS - 1 N2 - A majority of families with hereditary nonpolyposis colorectal cancer (HNPCC) are attributable to germline mutations in three DNA mismatch repair (MMR) genes, MLH1, MSH2 and MSH6. However, the clinical phenotype appears to reflect a complex interplay between the predisposing mutation and putative constitutional and somatic modifiers. Certain MMR gene mutations predispose to combined occurrence of cutaneous sebaceous gland neoplasms and visceral malignancies, which is known as Muir-Torre syndrome (MTS) and regarded as a phenotypic variant of HNPCC. The sebaceous tumors associated with MTS appear in many patients before visceral malignancies providing important predictability of HNPCC-related integral cancers in mutation carriers. Since most sebaceous skin tumors are, however, sporadic, the contribution of non-truncating mutations found in skin cancer patients is difficult to interpret and genetic assessment of MTS requires a functional test. Here, we studied the repair efficiency of the two MSH2 missense mutations, L187P and C697F, found in HNPCC families including a few mutation carriers with sebaceous skin tumors. Both mutations were completely deficient in an MMR assay, which together with tumor findings suggested their predisposing role in both internal and skin malignancies in the families. SN - 1019-6439 UR - https://www.unboundmedicine.com/medline/citation/16327991/The_importance_of_functional_testing_in_the_genetic_assessment_of_Muir_Torre_syndrome_a_clinical_subphenotype_of_HNPCC_ L2 - http://www.spandidos-publications.com/ijo/28/1/149 DB - PRIME DP - Unbound Medicine ER -