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

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

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22 Scopus citations


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.

Original languageEnglish
Pages (from-to)149-153
Number of pages5
JournalInternational Journal of Oncology
Issue number1
StatePublished - Jan 2006
Externally publishedYes


All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Oncology

Cite this

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), 149-153.