Open AccessCharacterization of genetic lesions in rhabdomyosarcoma using a high‐density single nucleotide polymorphism array
Author(s) -
Nishimura Riki,
Takita Junko,
SatoOtsubo Aiko,
Kato Motohiro,
Koh Katsuyoshi,
Hanada Ryoji,
Tanaka Yukichi,
Kato Keisuke,
Maeda Daichi,
Fukayama Masashi,
Sanada Masashi,
Hayashi Yasuhide,
Ogawa Seishi
Publication year - 2013
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12173
Subject(s) - loss of heterozygosity , neuroblastoma ras viral oncogene homolog , biology , kras , rhabdomyosarcoma , locus (genetics) , brachyury , single nucleotide polymorphism , pathology , genetics , cancer research , allele , genotype , medicine , gene , sarcoma , mutation , mesoderm , embryonic stem cell
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 IRS 2 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 .