Cytogenetics of primary skin tumors

Skin tumors can arise as a result of cumulative genetic abnormalities, including chromosomal ­aberrations that can be described as either morphological (structural rearrangements) or molecular (copy number variations). Cytogenetic techniques have been used to examine both large and small chromosomal aberrations, and include karyotyping, comparative genomic hybridization, and fluorescence in situ hybridization. This chapter describes the recurrent aberrations associated with skin tumors, such as benign melanocytic nevi, melanoma, basal cell carcinoma, squamous cell carcinoma, actinic (solar) keratosis, Bowen’s disease, keratoacanthoma, Merkel cell carcinoma, dermatofibrosarcoma protuberans, and cutaneous lymphomas, as detected by cytogenetic methodologies. A significant number of genomic aberrations are shared across different subtypes of skin tumors, including structural and numerical alterations of chromosome 1, −3p, +3q, +6, +7, +8q, −9p, +9q, −10, −17p, +17q and +20. Aberrations specific to certain skin cancers have also been detected, and include: loss of 18q in squamous cell carcinoma, but not its precursor, actinic keratosis; loss of 9q22 in sporadic basal cell carcinoma; and translocation involving 17q22 and 22q13 in dermatofibrosarcoma protuberans. These regions contain a number of potential candidate genes that are involved in aspects of cell signaling, proliferation, differentiation, and apoptosis. Cytogenetic methodologies continue to evolve with the advent of array-based comparative genomic hybridization, copy number variation microarrays, and next-generation sequencing. It is envisioned that cytogenetic analysis will continue to be employed for identification and further exploration of novel chromosomal regions and associated genes that drive skin tumorigenesis.

Cytogenetics of melanoma and nonmelanoma skin cancer

Cytogenetic analysis of melanoma and nonmelanoma skin cancers has revealed recurrent aberrations, the frequency of which is reflective of malignant potential. Highly aberrant karyotypes are seen in melanoma, squamous cell carcinoma, solar keratosis and Merkel cell carcinoma with more stable karyotypes seen in basal cell carcinoma, keratoacanthoma, Bowen’s disease, dermatofibrosarcomarotuberans and cutaneous lymphomas. Some aberrations were common amongst a number of skin cancer types including rearrangements and numerical abnormalities of chromosome 1, −3p, +3q, partial or entire trisomy 6, trisomy 7, +8q, −9p, +9q, partial or entire loss of chromosome 10, −17p, + 17q and partial or entire gain of chromosome 20. Combination of cytogenetic analysis with other molecular genetic techniques has enabled the identification of not only aberrant chromosomal regions, but also the genes that contribute to a malignant phenotype. This review provides a comprehensive summary of the pertinent cytogenetic aberrations associated with a variety of melanoma and nonmelanoma skin cancers.

Cytogenetics of basal cell carcinoma and squamous cell carcinomas

Cytogenetic analysis is a powerful tool that allows analysis of chromosomal aberrations associated with diseased states. In particular, a combination of cytogenetic techniques has allowed the identification of aberrations associated with cancer development, including cancers of the skin. This chapter provides a comprehensive overview of cytogenetic alterations in basal and squamous cell carcinomas of the skin. These two distinct lesions have altered karyotypes that are consistent with their malignant potential. Basal cell carcinomas, although relatively stable lesions, are highly associated with recurrent aberrations of chromosomes 6, 7, 9 and X, as detected by a number of cytogenetic techniques. Squamous cell carcinomas, on the other hand are associated with a much higher degree of instability, involving aberrations of chromosomes 3, 7, 8, 11, 13, 17 and 18, as detected using a number of cytogenetic techniques. Overall, the numbers and types of aberrations associated with basal and squamous cell carcinoma, define the characteristic behaviour associated with these lesions and identification of these aberrations may aid in the understanding of malignant potential, prognosis and treatment of these skin cancers.

Candidate metastasis suppressor genes uncovered by array comparative genomic hybridization in a mouse allograft model of prostate cancer.

Background The purpose of this study was to identify candidate metastasis suppressor genes from a mouse allograft model of prostate cancer (NE-10). This allograft model originally developed metastases by twelve weeks after implantation in male athymic nude mice, but lost the ability to metastasize after a number of in vivo passages. We performed high resolution array comparative genomic hybridization on the metastasizing and non-metastasizing allografts to identify chromosome imbalances that differed between the two groups of tumors. Results This analysis uncovered a deletion on chromosome 2 that differed between the metastasizing and non-metastasizing tumors. Bioinformatics filters were employed to mine this region of the genome for candidate metastasis suppressor genes. Of the 146 known genes that reside within the region of interest on mouse chromosome 2, four candidate metastasis suppressor genes (Slc27a2, Mall, Snrpb, and Rassf2) were identified. Quantitative expression analysis confirmed decreased expression of these genes in the metastasizing compared to non-metastasizing tumors. Conclusion This study presents combined genomics and bioinformatics approaches for identifying potential metastasis suppressor genes. The genes identified here are candidates for further studies to determine their functional role in inhibiting metastases in the NE-10 allograft model and human prostate cancer.

Regional chromosomal assignment of human renin gene to 1q12→qter and use in linkage studies in Charcot-Marie-Tooth disease

The gene for renin, previously mapped to human chromosome 1, was further localized to 1q12 → qter using human-mouse somatic cell hybrid DNAs. The renin DNA probe used (λ HR5) could detect a HindIII restriction fragment length polymorphism. When used in studies of 12 informative families, no linkage could be found between the renin and Charcot-Marie-Tooth disease. Furthermore, an association of any renin allele with hypertension was not apparent.

In arrayed ranks array technology in the study of mesothelioma steven

Mesothelioma is a rare malignancy arising from mesothelial cells lining the pleura and peritoneum. Advances in modern technology have allowed the development of array based approaches to the study of disease allowing researchers the opportunity to study many genes or proteins in a high-throughput fashion. This review describes the current knowledge surrounding array based approaches with respect to mesothelioma research. © 2009 by the International Association for the Study of Lung Cancer.