The importance of functional testing in the genetic assessment of Muir-Torre syndrome, a clinical subphenotype of HNPCC

  • Authors:
    • Saara Ollila
    • Roslyn Fitzpatrick
    • Laura Sarantaus
    • Reetta Kariola
    • Ingrid Ambus
    • Lea Velsher
    • Eugene Hsieh
    • Mette Klarskov Andersen
    • Tiina E. Raevaara
    • Anne-Marie Gerdes
    • Elisabeth Mangold
    • Päivi Peltomäki
    • Henry T. Lynch
    • Minna Nyström
  • View Affiliations

  • Published online on: January 1, 2006     https://doi.org/10.3892/ijo.28.1.149
  • Pages: 149-153
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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.

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January 2006
Volume 28 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Ollila S, Fitzpatrick R, Sarantaus L, Kariola R, Ambus I, Velsher L, Hsieh E, Andersen MK, Raevaara TE, Gerdes A, Gerdes A, et al: The importance of functional testing in the genetic assessment of Muir-Torre syndrome, a clinical subphenotype of HNPCC. Int J Oncol 28: 149-153, 2006
APA
Ollila, S., Fitzpatrick, R., Sarantaus, L., Kariola, R., Ambus, I., Velsher, L. ... 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, 149-153. https://doi.org/10.3892/ijo.28.1.149
MLA
Ollila, S., Fitzpatrick, R., Sarantaus, L., Kariola, R., Ambus, I., Velsher, L., Hsieh, E., Andersen, M. K., Raevaara, T. E., Gerdes, A., Mangold, E., Peltomäki, P., Lynch, H. T., Nyström, M."The importance of functional testing in the genetic assessment of Muir-Torre syndrome, a clinical subphenotype of HNPCC". International Journal of Oncology 28.1 (2006): 149-153.
Chicago
Ollila, S., Fitzpatrick, R., Sarantaus, L., Kariola, R., Ambus, I., Velsher, L., Hsieh, E., Andersen, M. K., Raevaara, T. E., Gerdes, A., Mangold, E., Peltomäki, P., Lynch, H. T., Nyström, M."The importance of functional testing in the genetic assessment of Muir-Torre syndrome, a clinical subphenotype of HNPCC". International Journal of Oncology 28, no. 1 (2006): 149-153. https://doi.org/10.3892/ijo.28.1.149