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

    Research output: Contribution to journalArticleScientificpeer-review

    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.
    Original languageEnglish
    JournalInternational Journal of Oncology
    Volume28
    Pages (from-to)149-153
    Number of pages5
    ISSN1019-6439
    Publication statusPublished - 2006
    MoE publication typeA1 Journal article-refereed

    Cite this

    Ollila, Saara ; Fitzpatrick, Roslyn ; Sarantaus, Laura ; Kariola, Reetta ; Ambus, Ingrid ; Velsher, Lea ; Hsieh, Eugene ; Klarskov-Andersen, Mette ; Raevaara, Tiina E ; Gerdes, Anne-Marie ; Mangold, Elisabeth ; Peltomäki, Päivi ; Lynch, Henry T ; Nyström, Minna. / The importance of functional testing in the genetic assessment of Muir-Torre syndrome, a clinical subphenotype of HNPCC. In: International Journal of Oncology. 2006 ; Vol. 28. pp. 149-153.
    @article{b297432d2692400ab39c81499ad92b7b,
    title = "The importance of functional testing in the genetic assessment of Muir-Torre syndrome, a clinical subphenotype of HNPCC",
    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.",
    author = "Saara Ollila and Roslyn Fitzpatrick and Laura Sarantaus and Reetta Kariola and Ingrid Ambus and Lea Velsher and Eugene Hsieh and Mette Klarskov-Andersen and Raevaara, {Tiina E} and Anne-Marie Gerdes and Elisabeth Mangold and P{\"a}ivi Peltom{\"a}ki and Lynch, {Henry T} and Minna Nystr{\"o}m",
    year = "2006",
    language = "English",
    volume = "28",
    pages = "149--153",
    journal = "International Journal of Oncology",
    issn = "1019-6439",
    publisher = "DEMETRIOS A./SPANDIDOS ED. & PUB",

    }

    Ollila, S, Fitzpatrick, R, Sarantaus, L, Kariola, R, Ambus, I, Velsher, L, Hsieh, E, Klarskov-Andersen, M, Raevaara, TE, Gerdes, A-M, Mangold, E, Peltomäki, P, Lynch, HT & 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, vol. 28, pp. 149-153.

    The importance of functional testing in the genetic assessment of Muir-Torre syndrome, a clinical subphenotype of HNPCC. / Ollila, Saara; Fitzpatrick, Roslyn; Sarantaus, Laura; Kariola, Reetta; Ambus, Ingrid; Velsher, Lea; Hsieh, Eugene; Klarskov-Andersen, Mette; Raevaara, Tiina E; Gerdes, Anne-Marie; Mangold, Elisabeth; Peltomäki, Päivi; Lynch, Henry T; Nyström, Minna.

    In: International Journal of Oncology, Vol. 28, 2006, p. 149-153.

    Research output: Contribution to journalArticleScientificpeer-review

    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 - Klarskov-Andersen, Mette

    AU - Raevaara, Tiina E

    AU - Gerdes, Anne-Marie

    AU - Mangold, Elisabeth

    AU - Peltomäki, Päivi

    AU - Lynch, Henry T

    AU - Nyström, Minna

    PY - 2006

    Y1 - 2006

    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.

    AB - 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.

    M3 - Article

    VL - 28

    SP - 149

    EP - 153

    JO - International Journal of Oncology

    JF - International Journal of Oncology

    SN - 1019-6439

    ER -