Assessment of the clinical and molecular impact of different cytogenetic subgroups in a series of 272 lipomas with abnormal karyotype

Abstract

Conventional lipomas harbor karyotypic changes that could be subdivided into four, usually mutually exclusive, categories: rearrangement, in particular through translocations, of chromosome bands 12q13-15, resulting in deregulation of the HMGA2 gene, loss of material from or rearrangement of chromosome 13, supernumerary ring or giant marker chromosomes, and aberrations of chromosome band 6p21. In the present study, 272 conventional lipomas, two-thirds of them deep-seated, with acquired clonal chromosome changes were assessed with regard to karyotypic and clinical features. A nonrandom distribution of breakpoints and imbalances could be confirmed, with 83% of the cases harboring one or more of the previously known cytogenetic hallmarks. Correlation with clinical features revealed that lipomas with rings/giant markers were larger, occurred in older patients, were more often deep-seated, and seemed to have an increased tendency to recur locally, compared with tumors with other chromosome aberrations. The possible involvement of the HMGA2 gene in cases that did not show any of the characteristic cytogenetic changes was further evaluated by locus-specific metaphase fluorescence in situ hybridization (FISH) and RT-PCR, revealing infrequent cryptic disruption of the gene but abundant expression of full length or truncated transcripts. By FISH, we could also show that breakpoints in bands 10q22-23 do not affect the MYST4 gene, whereas breakpoints in 6p21 or 8q11-12 occasionally target the HMGA1 or PLAG1 genes, respectively, also in conventional lipomas.

Cytogenetics of Spindle Cell/Pleomorphic Lipomas: Karyotyping and FISH Analysis of 31 Tumors

“…Our findings show that structural CANCER GENOMICS & PROTEOMICS 15: 193-200 (2018) 196 Deletions of 13q or loss of chromosome 13 were also reported in ordinary lipomas with karyotypic aberrations, albeit less frequently (16,17,27,28). In the Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer, 12 lipomas with -13 and 35 lipomas with del(13q) are listed (29).…”

Value and limitation of immunohistochemical expression of HMGA2 in mesenchymal tumors: about a series of 1052 cases

“…HMGA2 is certainly the important gene of this rearrangement in lipomas 3,4 as there are no fewer than 41 other chromosomal loci as partners of HMGA2. 3,30,31 However, conventional lipomas with normal karyotypes 31 or with aberrations in 6p21 or on chromosome 13q have been reported. These data could explain that in our series, roughly 14% of conventional lipomas do not express HMGA2.…”

Duplication of chromosome segment 12q13-15 in a lipomatous tumor with minimal nuclear atypia: A case report

“…Ordinary lipomas harbor translocations of 12q13-15, loss of 13q or rearrangements of 6p21 (3). The most frequent translocation is t(3;12)(q27-28;q13-15), observed in ~25% of cases with 12q13-15 alterations (12).…”

“…Overall, ~75% of ordinary lipomas harbor chromosomal rearrangements of 12q13-15, resulting in deregulation of the high mobility group AT-hook 2 (HMGA2) gene (3). By contrast, the cytogenetic hallmark of ALT is the presence of one or more supernumerary ring or giant marker chromosomes (4).…”