Genetic aberrations detected by comparative genomic hybridisation in vulvar cancers

Abstract

Squamous cell carcinoma of the vulva is a disease of significant clinical importance, which arises in the presence or absence of human papillomavirus. We used comparative genomic hybridisation to document non-random chromosomal gains and losses within human papillomavirus positive and negative vulvar cancers. Gain of 3q was significantly more common in human papillomavirus-positive cancers compared to human papillomavirus-negative cancers. The smallest area of gain was 3q22 -25, a chromosome region which is frequently gained in other human papillomavirus-related cancers. Chromosome 8q was more commonly gained in human papillomavirus-negative compared to human papillomavirus-positive cancers. 8q21 was the smallest region of gain, which has been identified in other, non-human papillomavirus-related cancers. Chromosome arms 3p and 11q were lost in both categories of vulvar cancer. This study has demonstrated chromosome locations important in the development of vulvar squamous cell carcinoma. Additionally, taken together with previous studies of human papillomaviruspositive cancers of other anogenital sites, the data indicate that one or more oncogenes important in the development and progression of human papillomavirus-induced carcinomas are located on 3q. The different genetic changes seen in human papillomavirus-positive and negative vulvar squamous cell carcinomas support the clinicopathological data indicating that these are different cancer types.

An Integrative Approach Uncovers Biomarkers that Associate with Clinically Relevant Disease Outcomes in Vulvar Carcinoma

“…However, most studies are not comparable with our findings, because they extracted DNA from FFPE (12, 13) or cell lines (14,15). Furthermore, some studies controlled for HPV, used disparate methods or lower-resolution platforms (12)(13)(14)(15).…”

“…Gains in the long arm of chromosome 3 were frequent in our casuistic, which is a common finding in studies on VSCC (12)(13)(14)(15) and other solid tumors (24). However, the normally concomitant findings with this imbalance (e.g., gains in chr8q and losses in chr3p and chr8p) were not observed.…”

“…Wide-coverage methods, such as chromosomal and array comparative genomic hybridization (aCGH), have been used in several studies to better understand VSCC, reporting gains in 3q and 8q and losses in 3p and 8q as recurrent alterations (12)(13)(14)(15)(16). Despite these findings, most of these studies used lower-resolution CGH approaches (12)(13)(14); two used FFPE samples, which can lead to data misinterpretation (12,13); and none validated the observed alterations.…”

“…Despite these findings, most of these studies used lower-resolution CGH approaches (12)(13)(14); two used FFPE samples, which can lead to data misinterpretation (12,13); and none validated the observed alterations.…”

High-resolution genomic profiling of human papillomavirus-associated vulval neoplasia

“…Limited data are available on the genetic alterations associated with VSCC and VIN precursor lesions; previous studies have used microsatellite marker analysis and metaphase comparative genomic hybridisation (CGH) rather than higher resolution arraybased techniques (Pinto et al, 1999;Jee et al, 2001;Rosenthal et al, 2001;Allen et al, 2002;Micci et al, 2003;Bryndorf et al, 2004;Huang et al, 2005). In contrast, the genetic changes associated with CIN and CxSCC have been extensively studied, most recently using array-based methods (Hidalgo et al, 2005;Wilting et al, 2006Wilting et al, , 2009Choi et al, 2007;Kloth et al, 2007;Scotto et al, 2008a, b).…”