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 language | English |
|---|---|
| Pages (from-to) | 149-153 |
| Number of pages | 5 |
| Journal | International Journal of Oncology |
| Volume | 28 |
| Issue number | 1 |
| State | Published - Jan 2006 |
| Externally published | Yes |
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All Science Journal Classification (ASJC) codes
- Cancer Research
- Oncology
Cite this
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; Andersen, Mette Klarskov; Raevaara, Tiina E.; Gerdes, Anne Marie; Mangold, Elisabeth; Peltomäki, Päivi; Lynch, Henry T.; Nyström, Minna.
In: International Journal of Oncology, Vol. 28, No. 1, 01.2006, p. 149-153.Research output: Contribution to journal › Article
}
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 - 2006/1
Y1 - 2006/1
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.
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.
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M3 - Article
VL - 28
SP - 149
EP - 153
JO - International Journal of Oncology
JF - International Journal of Oncology
SN - 1019-6439
IS - 1
ER -