Genome‐wide approach to identify second gene targets for malignant rhabdoid tumors using high‐density oligonucleotide microarrays. Issue 3 (26th February 2014)

• Record Type: Journal Article
• Authors: Takita, Junko; Chen, Yuyan; Kato, Motohiro; Ohki, Kentaro; Sato, Yusuke; Ohta, Shigeru; Sugita, Kanji; Nishimura, Riki; Hoshino, Noriko; Seki, Masafumi; Sanada, Masashi; Oka, Akira; Hayashi, Yasuhide; Ogawa, Seishi
• Is Part Of: Cancer science. Volume 105:Issue 3(2014:Mar.)
• Page Start: 258
• Page End: 264
• Publication Date: 2014-02-26
• Subjects: Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.12352
• Languages: English
• ISSNs: 1347-9032

Abstract

<abstract abstract-type="main" id="cas12352-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Malignant rhabdoid tumor (MRT) is a rare and highly lethal cancer that mainly affects infants and young children. The majority of MRT are characterized by loss of function of <italic>SMARCB1</italic> on chromosome 22q11.2. However, little is known about genetic changes other than <italic>SMARCB1</italic> alterations that are responsible for the development and/or progression of MRT. To explore additional gene targets in MRT, we analyzed 21 MRT specimens (12 fresh tumors and 9 MRT‐derived cell lines) using high‐density single nucleotide polymorphism genotyping microarrays. Although MRT genomes are characterized by common 22q11.2 deletions, affecting the <italic>SMARCB1</italic> locus with a frequency of 95.2% (20/21 specimens), other genetic changes have been less frequent. Of the 20 specimens with deletions of 22q11.2, eight specimens showed uniparental disomy of the <italic>SMARCB1</italic> locus with homozygous deletions or gene mutations. High‐resolution analysis also disclosed the recurrent hemizygous/homozygous deletions of 7q35–q36.1, involving the <italic>CNTNAP2</italic> locus in three specimens. Mutations analysis of <italic>CNTNAP2</italic> showed a novel R157C missense mutation in a primary case, and methylation analysis showed recurrent hypermethylation of <italic>CNTNAP2</italic> in three of nine cell lines. These results demonstrated that <italic>CNTNAP2</italic> is one of the additional gene targets, other than <italic>SMARCB1</italic>, in MRT.</p> </abstract>