hMLH1 and hMSH2 gene mutations are present in radial growth-phase cutaneous malignant melanoma cell lines and can be induced further by ultraviolet-B irradiation.

Abstract:

:Microsatellite instability and reduced expression of mismatch repair proteins were reported in melanomas. However, little is known about mutational changes of the mismatch repair genes in radial growth-phase melanoma especially following UVB irradiation. To investigate these changes, an in vitro system consisting of radial growth-phase Wistar melanoma cell lines (WM35, WM3211 and WM1650) was established. The cells were UVB irradiated (10 mJ/cm(2)), and evaluated for mutational changes of exon regions 13,16 and 19 (hMLH1) and 6,7 and 12 (hMLH2) of these genes before and after irradiation. The genomic DNAs were PCR amplified and the products were directly sequenced. Transition (C-->T, G-->A, T-->C) and transversion (G-->, A-->T) mutations were found in exons 6,16 and 19. Some were present in both the sham-irradiated and UV-irradiated cells but others were only detected after UVB irradiation. hMLH1 and hMLH2 gene mutations occur early in melanoma tumorigenesis. The ability of UVB irradiation to induce additional mutations in these repair genes suggests its possible role in melanoma pathogenesis. Further investigation will be needed to determine whether mutations such as these contribute to the development of microsatellite instability in melanoma.

journal_name

Exp Dermatol

journal_title

Experimental dermatology

authors

Hussein MR,Wood GS

doi

10.1111/j.0906-6705.2003.00104.x

subject

Has Abstract

pub_date

2003-12-01 00:00:00

pages

872-5

issue

6

eissn

0906-6705

issn

1600-0625

journal_volume

12

pub_type

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