Genetic alterations in main candidate genes during melanoma progression
نویسندگان
چکیده
Cutaneous melanoma is a common and aggressive human skin cancers. Much is actually known about the molecular mechanisms underlying melanoma pathogenesis. The aim of the study was to evaluate any possible correlation between mutations in main growth-controlling genes (BRAF, NRAS, CDKN2A) and copy number variations in frequently amplified candidate genes (MITF, EGFR, CCND1, cMET, and cKIT) during melanoma initiation and progression. A large series of primary and secondary melanoma tissue samples (N = 274) from 232 consecutively-collected patients of Italian origin as well as 32 tumor cell lines derived from primary and metastatic melanomas underwent mutation screening and fluorescence in situ hybridization (FISH) analysis. Overall, BRAF, NRAS, and CDKN2A were found mutated in 62.5%, 12.5% and 59% cell lines and in 47%, 16%, 12% tumor tissues, respectively. Quite identical mutation patterns between primary tumors and metastatic lesions were found for BRAF and NRAS genes; mutations of CDKN2A gene appeared to be instead selected during tumor progression. In cell lines, high rates of gene amplifications were observed (varying from 12.5% for cKIT to 50% for MITF); vast majority of cell lines (75%) presented at least one amplified gene. Conversely, prevalence of gene amplification was significantly and progressively decreasing in melanoma metastases (12%) and primary melanomas (4%). Our findings suggest that gene amplifications may be acquired during the late phases of melanoma evolution and mostly act as "passenger" or "non-causative" alterations.
منابع مشابه
Molecular genetic control of leaf lifespan in plants - A review
Leaf senescence constitutes the last stage of leaf development in plants and proceeds through a highly regulated program in order to redistribution of micro- and macro-nutrients from the senescing leaves to the developing/growing plant organs. Initiation and progression of leaf senescence is accompanied by massive sequential alterations at various levels of leaf biology including leaf morpholog...
متن کاملI-3: Tale of The Tail: Candidate Genes Involved in Sperm Flagella Formation
Background ISTS defect in which sperm tail is short and fibrous sheath and axoneme are disorganized, is one of the syndromes that cause male infertility. Although a few studies have been done in this regard, its exact etiology in human is unclear yet. Four candidate genes causing ISTS are SPEF2, RABL2B, and A-kinas anchoring proteins genes (AKAP3 and AKAP4). Proteins which coded by SPEF2 and RA...
متن کاملThe promise of microarray technology in melanoma care.
BACKGROUND Genetic aberration is responsible for the development of neoplastic potential in a number of malignancies. These DNA alterations result in significant changes in gene expression that may now be measured and catalogued. The microarray technique screens and identifies expressed genes that may be responsible for tumorigenesis. METHODS The authors review the application of the microarr...
متن کاملScreening for melanoma modifiers using a zebrafish autochthonous tumor model.
Genomic studies of human cancers have yielded a wealth of information about genes that are altered in tumors. A challenge arising from these studies is that many genes are altered, and it can be difficult to distinguish genetic alterations that drove tumorigenesis from that those arose incidentally during transformation. To draw this distinction it is beneficial to have an assay that can quanti...
متن کاملDelving into somatic variation in sporadic melanoma.
Melanoma, the most aggressive form of skin cancer, has increased in incidence more rapidly than any other cancer. The completion of the human genome project and advancements in genomics technologies has allowed us to investigate genetic alterations of melanoma at a scale and depth that is unprecedented. Here, we survey the history of the different approaches taken to understand the genomics of ...
متن کامل