Basal cell carcinoma of the skin: whole genome screening by comparative genome hybridization revisited

Abstract

Basal cell carcinoma (BCC) of the skin is considered to be the most common malignancy in people of European ancestry. It is often not clinically aggressive and has been regarded as genetically stable. However, histopathologic subtypes of BCC differ in their ability to invade surrounding tissues and recur. The aim of this work was to present a comprehensive study of chromosomal imbalances of cutaneous BCC and to correlate the findings with their histopathologic and clinical features. In all, 101 tumor samples were classified according to the current microscopic classification of BCC and then analyzed by comparative genomic hybridization (CGH). Over 60% of BCC were found to carry chromosomal imbalances - partial or whole chromosome gains and losses. Different subtypes of BCC presented common chromosomal alterations. No single chromosomal imbalance was found to be characteristic of a particular subtype of BCC, although the frequency of some chromosomal changes differed from one group to the other. The significance of chromosome 2 gains as a phenomenon that does not coexist with the losses in 9q is discussed.

Genomic Analysis of Smoothened Inhibitor Resistance in Basal Cell Carcinoma

“…This alteration has not been observed previously in untreated BCCs (Pesz et al, 2013) and therefore might only provide a selective advantage in the presence of a SMO inhibitor. Strikingly, both copies of PTEN were lost in one case, suggesting this may not be a passenger CNV.…”

Comparative genomic hybridization analysis of basal cell carcinoma

“…Trisomy 6 was only observed in two (15.4 %) of our samples, whereas the frequency varied from 19 % to 38 % in other studies [5][6][7] . In our series, gains of the region 6p21.1 were detected in 54 % of BCC cases, a rate similar to the 47 % previously reported for the region 6pter-p21 [ 4 ] .…”

“…Histological subtype Sun exposed area * Age/Gender Aneuploidies To our knowledge, there have been two reports of chromosomal imbalances in cases of BCC using array-CGH [ 4,5 ] , but no regions of chromosomal gains or losses have been specifi ed. These two studies and our series confi rm the presence of aneuploidies in BCC samples.…”

Copy number variations in atypical fibroxanthomas and pleomorphic dermal sarcomas

“…Characteristic CNV have been identified in other UV-induced skin tumors such as malignant melanomas [ 3 ], cutaneous SCC [ 4 ] and BCC [ 5 ]. In only one previous study comparative genomic hybridization (CGH) revealed many shared CNVs in AFX and PDS (most frequently deletions on chromosomes 9p and 13q).…”

“…In addition to somatic mutations, copy number variations (CNV) by gain of specific chromosomal segments containing relevant oncogenes or loss of chromosomal segments harboring critical tumor suppressor genes have been shown to be highly characteristic of other UV-induced skin tumors such as malignant melanoma [ 3 ], cutaneous squamous cell carcinoma (SCC) [ 4 ] and basal cell carcinoma (BCC) [ 5 ]. The aim of the present study was to analyze CNV in a large sample cohort of AFX and PDS to get further insights into their evolutionary process as well as to detect additional diagnostic or therapeutic target structures.…”