title: Copy number alterations and neoplasia-specific mutations in MELK, PDCD1LG2, TLN1, and PAX5 at 9p in different neoplasias.
abstract: 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 CDKN2A 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 MELK and PDCD1LG2 genes. The most commonly mutated gene in sarcomas was TLN1 (8%) and PAX5 in ALL (9%). Mutations in PAX5, and RUSC2, were seen exclusively in ALL patients and those in KIAA1432, CA9, TLN1, and MELK only in sarcomas (MFH, FS, EFT). Thus using targeted NGS of the 9p region, in addition to commonly deleted CDKN2A 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.
authors.affiliation: Department of Pathology, Haartman Institute and HUSLAB, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Virinder Kaur
authors.initials: VK
authors.lastname: Sarhadi
authors.forename: Leo
authors.initials: L
authors.lastname: Lahti
authors.forename: Ilari
authors.initials: I
authors.lastname: Scheinin
authors.forename: Pekka
authors.initials: P
authors.lastname: Ellonen
authors.forename: Eeva
authors.initials: E
authors.lastname: Kettunen
authors.forename: Massimo
authors.initials: M
authors.lastname: Serra
authors.forename: Katia
authors.initials: K
authors.lastname: Scotlandi
authors.forename: Piero
authors.initials: P
authors.lastname: Picci
authors.forename: Sakari
authors.initials: S
authors.lastname: Knuutila
mesh_terms: D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D018628:Gene Dosage; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D051757:PAX5 Transcription Factor / Q000235:genetics*; D061027:Programmed Cell Death 1 Ligand 2 Protein / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D016608:Talin / Q000235:genetics*
chemical_list: D051757:PAX5 Transcription Factor; C497281:PAX5 protein, human; C556977:PDCD1LG2 protein, human; D061027:Programmed Cell Death 1 Ligand 2 Protein; C518832:TLN1 protein, human; D016608:Talin; C484610:MELK protein, human; D017346:Protein Serine-Threonine Kinases