Dataset Information

Characterization of genetic lesions in rhabdomyosarcoma using a high-density single nucleotide polymorphism array.

ABSTRACT: Rhabdomyosarcoma (RMS) is a common solid tumor in childhood divided into two histological subtypes, embryonal (ERMS) and alveolar (ARMS). The ARMS subtype shows aggressive clinical behavior with poor prognosis, while the ERMS subtype has a more favorable outcome. Because of the rarity, diagnostic diversity and heterogeneity of this tumor, its etiology remains to be completely elucidated. Thus, to identify genetic alterations associated with RMS development, we performed single nucleotide polymorphism array analyses of 55 RMS samples including eight RMS-derived cell lines. The ERMS subtype was characterized by hyperploidy, significantly associated with gains of chromosomes 2, 8 and 12, whereas the majority of ARMS cases exhibited near-diploid copy number profiles. Loss of heterozygosity of 15q was detected in 45.5% of ARMS that had been unrecognized in RMS to date. Novel amplifications were also detected, including IRS2 locus in two fusion-positive tumors, and KRAS or NRAS loci in three ERMS cases. Of note, gain of 13q was significantly associated with good patient outcome in ERMS. We also identified possible application of an ALK inhibitor to RMS, as ALK amplification and frequent expression of ALK were detected in our RMS cohort. These findings enhance our understanding of the genetic mechanisms underlying RMS pathogenesis and support further studies for therapeutic development of RMS.

SUBMITTER: Nishimura R

PROVIDER: S-EPMC7657110 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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Characterization of genetic lesions in rhabdomyosarcoma using a high-density single nucleotide polymorphism array.

Nishimura Riki R Takita Junko J Sato-Otsubo Aiko A Kato Motohiro M Koh Katsuyoshi K Hanada Ryoji R Tanaka Yukichi Y Kato Keisuke K Maeda Daichi D Fukayama Masashi M Sanada Masashi M Hayashi Yasuhide Y Ogawa Seishi S

Cancer science 20130523 7

Rhabdomyosarcoma (RMS) is a common solid tumor in childhood divided into two histological subtypes, embryonal (ERMS) and alveolar (ARMS). The ARMS subtype shows aggressive clinical behavior with poor prognosis, while the ERMS subtype has a more favorable outcome. Because of the rarity, diagnostic diversity and heterogeneity of this tumor, its etiology remains to be completely elucidated. Thus, to identify genetic alterations associated with RMS development, we performed single nucleotide polymor ...[more]

PMID: 23578105

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Project description:Italy counts a large number of local chicken populations, some without a recognized genetic structure, such as Val Platani (VPL) and Cornuta (COS), which represent noteworthy local genetic resources. In this study, the genotype data of 34 COS and 42 VPL, obtained with the Affymetrix Axiom600KChicken Genotyping Array, were used with the aim to investigate the genetic diversity, the runs of homozygosity (ROH) pattern, as well as the population structure and relationship within the framework of other local Italian and commercial chickens. The genetic diversity indices, estimated using different approaches, displayed moderate levels of genetic diversity in both populations. The identified ROH hotspots harbored genes related to immune response and adaptation to local hot temperatures. The results on genetic relationship and population structure reported a clear clustering of the populations according to their geographic origin. The COS formed a nonoverlapping genomic cluster and clearly separated from the other populations, but showed evident proximity to the Siciliana breed (SIC). The VPL highlighted intermediate relationships between the COS-SIC group and the rest of the sample, but closer to the other Italian local chickens. Moreover, VPL showed a complex genomic structure, highlighting the presence of 2 subpopulations that match with the different source of the samples. The results obtained from the survey on genetic differentiation underline the hypothesis that Cornuta is a population with a defined genetic structure. The substructure that characterizes the Val Platani chicken is probably the consequence of the combined effects of genetic drift, small population size, reproductive isolation, and inbreeding. These findings contribute to the understanding of genetic diversity and population structure, and represent a starting point for designing programs to monitor and safeguard these local genetic resources, in order to define a possible official recognition program as breeds.

Project description:We applied whole-genome single nucleotide polymorphism (SNP) arrays to define a comprehensive genetic profile of 23 esophageal adenocarcinoma (EAC) primary tumor biopsies based on loss of heterozygosity (LOH) and DNA copy number changes. Alterations were common, averaging 97 (range 23-208) per tumor. LOH and gains averaged 33 (range 3-83) and 31 (range 11-73) per tumor, respectively. Copy neutral LOH events averaged 27 (range 7-57) per EAC. We noted 126 homozygous deletions (HDs) across the EAC panel (range 0-11 in individual tumors). Frequent HDs within FHIT (17/23), WWOX (8/23) and DMD (6/23) suggest a role for common fragile sites or genomic instability in EAC etiology. HDs were also noted for known tumor suppressor genes (TSGs) including: CDKN2A, CDKN2B, SMAD4 and GALR1, and identified PDE4D and MGC48628 as potentially novel TSGs. All tumors showed LOH for most of chromosome 17p, suggesting that TSGs other than TP53 maybe targeted. Frequent gains were noted around MYC (13/23), BCL9 (12/23), CTAGE1 (14/23) and ZNF217 (12/23). Thus, we have confirmed previous reports indicating frequent changes to FHIT, CDKN2A, TP53 and MYC in EAC and identified additional genes of interest. Meta analysis of previous genome-wide EAC studies together with the data presented here, highlighted consistent regions of gain on 8q, 18q and 20q, and multiple LOH regions on 4q, 5q, 17p and 18q, suggesting that more than one gene may be targeted on each of these chromosome arms. The focal gains and deletions documented here are a step towards identifying the key genes involved in EAC development. Keywords: High Density SNP array Here we use Illumina 317K whole-genome single-nucleotide polymorphism arrays to define a comprehensive allelotype of melanoma based on loss of heterozygosity (LOH) and copy number changes in a panel of 23 esophageal adenocarcinoma (EAC) primary tumor biopsies. Each EAC was paired to normal squamous biopsy from 40328 (GSM266078) to generate the log_R_ratio.

Dataset Information

Characterization of genetic lesions in rhabdomyosarcoma using a high-density single nucleotide polymorphism array.

Publications

Characterization of genetic lesions in rhabdomyosarcoma using a high-density single nucleotide polymorphism array.

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