GADD153 is an independent prognostic factor in melanoma: immunohistochemical and molecular genetic analysis.
The main role of growth arrest and DNA damage-inducible (GADD) genes is to block proliferation at G1 and G2 checkpoints in response to DNA damage. The goal of this study was to examine the expression of GADD genes in primary melanomas with respect to prognosis. GADD34 was found in 73% of the primary melanomas investigated. GADD45 and GADD153 were positive in 60% and 80% of primary melanomas, respectively. Cox regression demonstrated that only GADD153 had any independent prognostic impact. We therefore decided to establish a PCR assay for detection of GADD153 in paraffin-embedded tissue. GADD153 deletion was found in 3/26 melanomas. None of the 3 cases with GADD153 deletion showed any expression of GADD153. Sequencing analysis detected polymorphism T-C at amino acid position 10 in 6/23 melanomas. In 6 cases with GADD153 polymorphism, GADD153 expression was found in 2 melanomas with a maximum GADD153 index of 10%. We postulate that the GADD gene family plays an important role in melanoma progression.
Korabiowska
M
M
Department of Cytopathology, Georg August University, Göttingen, Germany.
Cordon-Cardo
C
C
Betke
H
H
Schlott
T
T
Kotthaus
M
M
Stachura
J
J
Brinck
U
U
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000943:Antigens, Differentiation; D022762:CCAAT-Enhancer-Binding Proteins / Q000096:biosynthesis*; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D002648:Child; D018572:Disease-Free Survival; D005821:Genetic Techniques; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D008545:Melanoma / Q000175:diagnosis* / Q000378:metabolism* / Q000401:mortality; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011379:Prognosis; D016016:Proportional Hazards Models; D014176:Protein Biosynthesis; D054645:Protein Phosphatase 1; D011506:Proteins; D012044:Regression Analysis; D017422:Sequence Analysis, DNA; D013997:Time Factors; D051742:Transcription Factor CHOP; D014157:Transcription Factors / Q000096:biosynthesis*; D000097642:GADD45 Proteins
D000943:Antigens, Differentiation; D022762:CCAAT-Enhancer-Binding Proteins; D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D054645:Protein Phosphatase 1; D011506:Proteins; D051742:Transcription Factor CHOP; D014157:Transcription Factors; D000097642:GADD45 Proteins; C497249:DDIT3 protein, human; C087519:PPP1R15A protein, human