Disruption of chromosome 11 in canine fibrosarcomas highlights an unusual variability of CDKN2B in dogs

Abstract

Background: In dogs in the western world neoplasia constitutes the most frequently diagnosed cause of death. Although there appear to be similarities between canine and human cancers, rather little is known about the cytogenetic and molecular alterations in canine tumours. Different dog breeds are susceptible to different types of cancer, but the genetic basis of the great majority of these predispositions has yet to be discovered. In some retriever breeds there is a high incidence of soft tissue sarcomas and we have previously reported alterations of chromosomes 11 and 30 in two poorly differentiated fibrosarcomas. Here we extend our observations and present a case report on detail rearrangements on chromosome 11 as well as genetic variations in a tumour suppressor gene in normal dogs.

Dog models of naturally occurring cancer

“…Although some strains of mice have developed spontaneous STS, rodent models generally require induction of STS [28]. By contrast, dogs are an excellent model of STS because they have similar tumor genetic complexity to humans [29]. For instance, two poorly differentiated fibrosarcomas taken from Labrador Retrievers had large chromosomal rearrangements, amplifications and deletions similar to those observed in human fibrosarcoma [30].…”

“…Notably, these fibrosarcomas had loss of heterozygosity affecting cyclin-dependent kinase family 2A and 2B ( CDKN2A/CDKN2B) . Given that deletions of CDKN2A and CDKN2B have been reported in other cancer types, including STS in humans, this offers a novel target for discovering common pathways and genes affected in both dogs and humans that affects the development or progression of STS [29]. …”

Simultaneous Inactivation of the <i>p16, p15</i> and <i>p14</i> Genes Encoding Cyclin-Dependent Kinase Inhibitors in Canine T-Lymphoid Tumor Cells

“…It was difficult to design another primer for p15, because of the high homology of its exon 2 with that of the p16/p14 genes (98%). Further, polymorphism in exon 1 of the p15 gene was reported in normal dogs [1]. Indeed, the reported polymorphism in p15 exon 1 was also observed in CLbL-1, GL-1, UL-1, CL-1 and LN tissues by sequence analysis (data not shown).…”

“…Fourteen dogs (dogs nos. [1][2][3][4][5][6][7][8][9][10][11][12][13][14] with IgH rearrangement were included, and all were diagnosed with multicentric high-grade lymphoma. Primary tumor cell samples were obtained from the LN of these dogs by FNA.…”

“…FJ542309) [21]. In another study [1], the entire coding sequence of the canine p15 gene (Genbank accession no. NM_00114629) and partial sequence of the canine p14 gene (Genbank accession no.…”