TY - JOUR
T1 - Malignant melanoma in patients with hereditary nonpolyposis colorectal cancer
AU - Ponti, G.
AU - Losi, L.
AU - Pellacani, G.
AU - Wannesson, L.
AU - Cesinaro, A. M.
AU - Venesio, T.
AU - Petti, C.
AU - Seidenari, S.
PY - 2008/7
Y1 - 2008/7
N2 - Background: Malignant melanoma (MM) is the most aggressive skin cancer. Most MMs are sporadic, and in this setting an association with mismatch repair (MMR) gene mutations, typical of hereditary nonpolyposis colorectal cancer (HNPCC) tumours, has been proposed. Objectives: To characterize clinically and/or by molecular biology the patients with MM belonging to a cohort of 60 kindreds with HNPCC. Methods: Patients with HNPCC with a diagnosis of MM were studied by immunohistochemistry (IHC) on tumour tissue using antibodies to MLH1, MSH2, p16, β-catenin and E-cadherin, and by direct sequencing of MMR genes on germline DNA, and BRAF and NRAS on somatic DNA extracted from MM. Results: Nine cutaneous MMs were detected in the tumour spectrum of eight families with HNPCC. The median age at diagnosis was 46 years. In one HNPCC family the diagnosis of MM was made in two first-degree relatives fitting the clinical definition of familial melanoma. IHC and sequencing analysis showed an MSH2 mutation in one patient with MM. Conclusions: Dermatological surveillance should be recommended to families in which MM is diagnosed in at least one member, especially at a young age. The combination of MMR gene mutations and abnormalities of p16 or other molecular pathways is needed to induce melanocytic carcinogenesis in a familial setting as well as in sporadic MM.
AB - Background: Malignant melanoma (MM) is the most aggressive skin cancer. Most MMs are sporadic, and in this setting an association with mismatch repair (MMR) gene mutations, typical of hereditary nonpolyposis colorectal cancer (HNPCC) tumours, has been proposed. Objectives: To characterize clinically and/or by molecular biology the patients with MM belonging to a cohort of 60 kindreds with HNPCC. Methods: Patients with HNPCC with a diagnosis of MM were studied by immunohistochemistry (IHC) on tumour tissue using antibodies to MLH1, MSH2, p16, β-catenin and E-cadherin, and by direct sequencing of MMR genes on germline DNA, and BRAF and NRAS on somatic DNA extracted from MM. Results: Nine cutaneous MMs were detected in the tumour spectrum of eight families with HNPCC. The median age at diagnosis was 46 years. In one HNPCC family the diagnosis of MM was made in two first-degree relatives fitting the clinical definition of familial melanoma. IHC and sequencing analysis showed an MSH2 mutation in one patient with MM. Conclusions: Dermatological surveillance should be recommended to families in which MM is diagnosed in at least one member, especially at a young age. The combination of MMR gene mutations and abnormalities of p16 or other molecular pathways is needed to induce melanocytic carcinogenesis in a familial setting as well as in sporadic MM.
KW - Familial melanoma syndrome
KW - Hereditary nonpolyposis colorectal cancer
KW - Malignant melanoma
KW - Mismatch repair genes
KW - P16
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U2 - 10.1111/j.1365-2133.2008.08575.x
DO - 10.1111/j.1365-2133.2008.08575.x
M3 - Article
C2 - 18460031
AN - SCOPUS:45749100009
VL - 159
SP - 162
EP - 168
JO - British Journal of Dermatology
JF - British Journal of Dermatology
SN - 0007-0963
IS - 1
ER -