A novel and consistent amplicon at 13q31 associated with alveolar rhabdomyosarcoma

Abstract

Rhabdomyosarcomas are the most common soft‐tissue sarcoma found in children. The alveolar subtype is clinically more aggressive than the embryonal subtype. In addition to the presence of specific chromosome translocations and associated fusion gene products in a high proportion of the alveolar subtype, we previously showed that tumors with this histology frequently show evidence of genomic amplification. Here, we substantially extended the number of alveolar rhabdomyosarcoma samples examined by comparative genomic hybridization analysis. Regions of loss were noted, including the smallest overlapping regions corresponding to 16q, 17/17p, and 9q32–34, in 16%, 10%, and 10% of cases, respectively (44 primary samples/6 cell lines). Amplification or gain at 12q13–15 in the region of the MDM2/GLI1/SAS/CDK4 loci and 2p24 at the MYCN locus was found in 28% and 32% of cases, respectively. Single amplicons were found at locations that in other samples showed consistent gain, including the regions 5q15–23, 7q21–31, 11p11–14, 17q23–24, and 20q13, and amplification was found in two cases at 15q24–26. However, most striking was a novel region of amplification or gain at 13q31 in 19% of cases (51 primary samples/6 cell lines). This indicates that a gene or genes at 13q31 are significant in the development or progression of alveolar rhabdomyosarcoma. Genes Chromosomes Cancer 28:220–226, 2000. © 2000 Wiley‐Liss, Inc.

The Human Glioma-Associated Oncogene Homolog 1 (GLI1) Family of Transcription Factors in Gene Regulation and Diseases

“…None of the seven Ewing’s sarcomas contained GLI1 amplification [25]. Gordon et al [11] reported 28% of 44 primary tumors and six cell lines of alveolar rhabdomyosarcomas to contain amplified GLI1 gene. Analysis of 37 primary adult sarcomas by Stein et al revealed the absence of GLI1 amplification in this tumor cohort [26].…”

“…Human GLI1 gene amplification is also uncommon in most cancers even though it was initially identified as an amplified gene in a cancer cell line. However, the incidence rates for GLI1 amplification vary significantly with the highest frequency (28%) reported in alveolar rhabdomyosarcomas [11]. A number of polymorphic variants of the human GLI1 gene have been reported, with the majority of them localized within the non-coding regions.…”

MicroRNAs in rhabdomyosarcoma: pathogenetic implications and translational potentiality

“…One of the first studies on miRNAs expression in the clinical context of RMS focused on amplification of the 13q31-32 chromosomal region, which is amplified in a fraction of alveolar RMS patients [97] and includes the C13orf25 gene [98]. This gene contains the miR-17-92 cluster (miR-17, miR-19a, miR-19b, miR-20a, and miR-92), which is considered an onco-miR cluster in some tumor types and cross-talks with MYC , an oncogene amplified in about 20% of fusion-positive alveolar RMS.…”

Pediatric Rhabdomyosarcoma

“…The most commonly amplified genomic regions observed in PAX gene fusion–positive tumors are 2p24, containing the MYCN oncogene, and 12q13-q14, which includes CDK4 . 26 The amplification of MYCN , which occurs in 28% of fusion-positive cases, has been confined to a genomic region less than 1 Mb, including the same region frequently observed in neuroblastoma cases. 27 This region includes only 2 genes ( MYCN and DDX1 ) and is observed most commonly in PAX3 - FOXO1 fusion–positive RMS.…”

“…Other amplified regions in fusion-positive tumors include 15q24-26, 1p36, 13q31, 1q21, and 8q13-21. 26 The regions of 1p36, which encompasses the PAX7 locus, and 13q31, which includes MIR17HG , are associated specifically with PAX7-FOXO1 tumors.…”