Tumor genomes frequently contain somatic copy number alterations (SCNA) that can significantly perturb the manifestation level of affected genes and thus disrupt pathways controlling normal growth. candidate genes potentially involved in tumorigenesis. Since few of these alterations were recurrent across our samples we used a protein network-guided approach to determine whether any pathways were TLK2 enriched in SCNA-genes in one or more samples. From this unbiased genome-wide analysis we recognized 28 significantly enriched pathway modules. Assessment with two large self-employed melanoma SCNA datasets showed less than 10% overlap at the individual gene level but network-guided analysis revealed 66% shared pathways including all but three of the pathways identified in our data. Frequently altered pathways included WNT cadherin signalling angiogenesis and melanogenesis. Additionally our results emphasize the potential of the and gene products involved in angiogenesis and migration as possible therapeutic targets in melanoma. Our study demonstrates the utility of network-guided approaches for both large and Indirubin small datasets to identify pathways recurrently perturbed in cancer. Introduction Somatic copy number alterations (SCNA) are a recurrent characteristic of malignant cancers   . The amplification and subsequent over-expression or conversely deletion and loss of expression of key regulators of cell proliferation senescence or death have been shown in many cases to contribute significantly to the progression from the normal to the malignant state    . Therefore the discovery and characterization of chromosomal regions involved in SCNA and of the genes encoded in them has been a crucial contributor to our understanding of the molecular mechanisms of carcinogenesis. The methods used to detect and characterize SCNA have evolved significantly over the last decades. Initial cytogenetic observations have been supplemented with Southern blots and quantitative PCR. Almost twenty years ago the availability of BAC clones delineating a tiling path through the entire human genome made it possible to detect SCNA in a genome-wide fashion but with limited resolution . More recently oligonucleotide-based arrays have enabled comparative genome hybridizations (CGH) at high resolution and CGH has become Indirubin the method of choice to detect copy-number variations   . A recent SNP-based survey  of 3 131 copy-number profiles derived from over 26 different types of cancer has provided a dramatic illustration of the power of high-throughput methods in distinguishing arbitrary modifications in the genome from the ones that may possess a direct effect on tumorigenesis. Genomic modifications in lots of tumors specifically at late phases in their advancement are so intensive how the copy-number position of specific genes or chromosomal areas may differ over Indirubin an extremely wide variety of values. An assortment of chromosomal rearrangements and focal expansions can create genomic scenery that have become difficult to investigate using regular CGH techniques. Furthermore the exact limitations of SCNA or the manifestation status from the Indirubin genes encoded within them are often as yet not known precluding an intensive evaluation of their effect on the phenotype from the tumor cells. It has been suggested that SNP arrays could be better fitted to the dedication of copy quantity areas in tumor examples because the evaluation of data produced from such arrays could make Indirubin usage of allelic imbalance info furthermore to hybridization strength . In today’s study we examined the genome-wide copy-number position of seven extremely aneuploid metastatic melanoma cell lines and established the manifestation of their genes utilizing a sequencing-based strategy. We show a mix of SNP-based and CGH arrays is essential to secure a dependable estimate of the real copy-number position of the complete genome when confronted with intensive genomic instability which the mix of copy-number and manifestation status provides effective clues regarding the feasible part of genes encoded within SCNA in tumorigenesis. Furthermore we show a protein-based network-guided evaluation of SCNA-affected genes with modified manifestation inside our data and two released datasets   recognizes pathways.