Altered molecular pathways in melanocytic lesions.
To identify gene expression changes in melanocytic lesions, biopsies from 18 common nevi (CMN), 11 dysplastic nevi (DN), 8 radial and 15 vertical growth phase melanomas (RGPM, VGPM), and 5 melanoma metastases (MTS) were analyzed using whole genome microarrays. The comparison between CMN and RGPM showed an enrichment of Gene Ontology terms related to inter and intracellular junctions, whereas the transition from RGPM to VGPM underlined the alteration of apoptosis. Upregulation of genes involved in dsDNA break repair and downregulation of cellular adhesion genes were observed in MTS with respect to VGPM. DN exhibited rather heterogeneous molecular profiles, with some proliferation genes expressed at higher levels than in CMN, altered regulation of transcription compared to RGPM and a subset of processes, such as mismatch repair, equally expressed as in VGPM. Furthermore, the expression profile of genes involved into cellular detoxification and antigen presentation split them into two classes, with different proliferation potential. Finally, molecular profiling of individual lesions identified altered biological processes, such as regulation of apoptosis, regulation of transcription and T-cell activation, not associated with specific histological classes but rather with subgroups of samples without apparent relationship. This holds true for dysplastic nevi in particular. Our data indicate that generally the intersection between stage specific and sample specific molecular alterations may lead to a more precise determination of the individual progression risk of melanocytic lesions.
Scatolini
Maria
M
Cancer Genomics Lab, Fondo Edo Tempia, Biella, Italy.
Grand
Maurizia Mello
MM
Cancer Genomics Lab, Fondo Edo Tempia, Biella, Italy.
Grosso
Enrico
E
Cancer Genomics Lab, Fondo Edo Tempia, Biella, Italy.
Venesio
Tiziana
T
Unit of Pathology, Institute for Cancer Research and Treatment (IRCC), Candiolo, Torino, Italy.
Pisacane
Alberto
A
Unit of Pathology, Institute for Cancer Research and Treatment (IRCC), Candiolo, Torino, Italy.
Balsamo
Antonella
A
Unit of Pathology, Institute for Cancer Research and Treatment (IRCC), Candiolo, Torino, Italy.
Sirovich
Roberta
R
Department of Mathematics, University of Torino, Torino, Italy.
Risio
Mauro
M
Unit of Pathology, Institute for Cancer Research and Treatment (IRCC), Candiolo, Torino, Italy.
Chiorino
Giovanna
G
Cancer Genomics Lab, Fondo Edo Tempia, Biella, Italy.
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D009506:Nevus / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology