Exonic deletions of mismatch repair genes MLH1 and MSH2 correlate with prognosis and protein expression levels in malignant melanomas.
The mutations of MLH1 and MSH2 have been reported to be responsible for malignant transformation and tumour progression in several sporadic tumours. Eighty-six primary malignant melanomas with known follow-up were investigated. Point mutations of DNA mismatch repair MLH1 and MSH2 in malignant melanomas were not found. Exon 12 (MSH2) was not present in 26 out of the 86 melanomas and exon 13 (MSH2) was lost in 25 of the tumours. The loss of exon 15 (MLH1) was observed in 22 out of the 86 tumours and the loss of exon 16 (MLH1) in 24 melanomas. The loss of exons correlated strongly with the loss of MLH1 and MSH2 protein expression. In multivariate analysis, including all 4 exons and expressions of MLH1 and MSH2, prognostic significance was found only for loss of exon 12 (MSH2) and loss of exon 15 (MLH1).
Korabiowska
Monika
M
Institute of Pathology, Reinhard Nieter Hospital, Academic Hospital of the University of Göttingen, Friedrich Paffrath Str. 100, 26389 Wilhelmshaven, Germany. korabmon@yahoo.de
Brinck
Ulrich
U
Stachura
Jerzy
J
Jawien
Jacek
J
Hasse
Frank Michael
FM
Cordon-Cardos
Carlos
C
Fischer
Gösta
G
D048868:Adaptor Proteins, Signal Transducing; D020137:Base Pair Mismatch; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D005091:Exons; D017353:Gene Deletion; D006801:Humans; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000096:biosynthesis / Q000235:genetics*; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics*; D017354:Point Mutation; D011379:Prognosis; D016016:Proportional Hazards Models; D015996:Survival Rate
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein