Cytogenetic alterations in nonmelanoma skin cancer: A review

Abstract

Since the advent of cytogenetic analysis, knowledge about fundamental aspects of cancer biology has increased, allowing the processes of cancer development and progression to be more fully understood and appreciated. Classical cytogenetic analysis of solid tumors had been considered difficult, but new advances in culturing techniques and the addition of new cytogenetic technologies have enabled a more comprehensive analysis of chromosomal aberrations associated with solid tumors. Our purpose in this review is to discuss the cytogenetic findings on a number of nonmelanoma skin cancers, including squamous- and basal cell carcinomas, keratoacanthoma, squamous cell carcinoma in situ (Bowen's disease), and solar keratosis. Through classical cytogenetic techniques, as well as fluorescence-based techniques such as fluorescence in situ hybridization and comparative genomic hybridization, numerous chromosomal alterations have been identified. These aberrations may aid in further defining the stages and classifications of nonmelanoma skin cancer and also may implicate chromosomal regions involved in progression and metastatic potential. This information, along with the development of newer technologies (including laser capture microdissection and comparative genomic hybridization arrays) that allow for more refined analysis, will continue to increase our knowledge about the role of chromosomal events at all stages of cancer development and progression and, more specifically, about how they are associated with nonmelanoma skin cancer.

GLI2 induces genomic instability in human keratinocytes by inhibiting apoptosis

“…Several studies have provided evidence of GIN in BCCs, highlighting their multiclonal nature and the presence of numerical chromosomal alterations, gene amplification, multinucleated cells and chromosome polysomy. 9, 10, 11, 12, 13, 14, 15 The development of BCC is associated with aberrant activation of the Hedgehog (HH) signalling pathway, which leads to increased expression and activation of glioma (GLI; GLI1 and GLI2) transcription factors, the principal effectors of the HH pathway. 16 Targeted expression of an active mutant of GLI2 (GLI2ΔN – a constitutively active form of GLI2 isoform β , lacking the N-terminal repressor domain) is sufficient to induce the formation of BCC-like lesions in the epidermis of transgenic mice 17, 18, 19 and is required for their maintenance.…”

Deciphering Squamous Cell Carcinoma Using Multidimensional Genomic Approaches

“…SqCC is associated with significant chromosomal aberrations at all stages of progression (reviewed in [133, 134]). In general, SqCC has increased genomic instability with 25%–90% of tumors demonstrating DNA aneuploidy.…”

Molecular Signatures Linked With Aggressive Behavior in Basal Cell Carcinoma: A Report of 6 Cases

“…12 With BCC, LOH has been detected in the genetic regions 1q, 22q, and most frequently in 9q22. 11 Interestingly, the tumor suppressor PTCH gene maps to this exact location on chromosome 9q. 13 Data on LOH in sporadic BCCs at chromosome 9q22 have been found to range from 30% to 90% 14 and LOH has been implicated in the involvement of the PTCH gene in the tumorigenesis of BCC.…”