Copy number alterations and neoplasia‐specific mutations in MELK, PDCD1LG2, TLN1, and PAX5 at 9p in different neoplasias. Issue 7 (24th March 2014)

• Record Type: Journal Article
• Authors: Sarhadi, Virinder Kaur; Lahti, Leo; Scheinin, Ilari; Ellonen, Pekka; Kettunen, Eeva; Serra, Massimo; Scotlandi, Katia; Picci, Piero; Knuutila, Sakari
• Is Part Of: Genes, chromosomes & cancer. Volume 53:Issue 7(2014:Jul.)
• Page Start: 579
• Page End: 588
• Publication Date: 2014-03-24
• Subjects: Cancer -- Genetic aspects -- Periodicals; 616.994042
• DOI: 10.1002/gcc.22168
• Languages: English
• ISSNs: 1045-2257

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Genetic alterations affecting 9p are commonly present in many cancer types and many cancer‐related genes are located in this chromosomal region. We sequenced all of the genes located in a 32Mb region of 9p by targeted next generation sequencing (NGS) in 96 patients with different cancer types, including acute lymphoblastic leukemia, bone malignant fibrous histiocytoma/undifferentiated pleomorphic sarcoma, fibrosarcoma, Ewing's sarcoma, and lung carcinoma. Copy number alterations (CNA), and mutations were studied from the NGS data. We detected a deletion at the <italic>CDKN2A</italic> locus as being the most frequent genetic alteration in all cancer types. In addition to this locus, NGS also identified other small regions of copy number loss and gain. However, different cancer types did not reveal any statistically significant differences with regard to CNA frequency or type. Of the 191 genes within the target region, two novel recurrent mutations were found in the <italic>MELK</italic> and <italic>PDCD1LG2</italic> genes. The most commonly mutated gene in sarcomas was <italic>TLN1</italic> (8%) and <italic>PAX5</italic> in ALL (9%). Mutations in <italic>PAX5</italic>, and <italic>RUSC2</italic>, were seen exclusively in ALL patients and those in <italic>KIAA1432, CA9, TLN1</italic>, and <italic>MELK</italic> only in sarcomas (MFH, FS, EFT). Thus using targeted NGS of the 9p region, in addition to commonly deleted <italic>CDKN2A</italic> locus, we were able to identify a number of small deletions and gains, as well as novel recurrent mutations in different cancer types. © 2014 Wiley Periodicals, Inc.</p> </abstract>