title: Heterogeneity of 11q13 region rearrangements in laryngeal squamous cell carcinoma analyzed by microarray platforms and fluorescence in situ hybridization.
abstract: We reinvestigated rearrangements occurring in region q13 of chromosome 11 aiming to: (i) describe heterogeneity of the observed structural alterations, (ii) estimate amplicon size and (iii) identify of oncogenes involved in laryngeal cancer progression as potential targets for therapy. The study included 17 cell lines derived from laryngeal cancers and 34 specimens from primary laryngeal tumors. The region 11q13 was analyzed by fluorescence in situ hybridization (FISH), array comparative genomic hybridization (aCGH) and gene expression microarray. Next, quantitative real time PCR was used for chosen genes to confirm results from aCGH and gene expression microarray. The observed pattern of aberrations allows to distinguish three ways, in which gain and amplification involving 11q13 region may occur: formation of a homogeneously staining region; breakpoints in/near 11q13, which lead to the three to sevenfold increase of the copy number of 11q13 region; the presence of additional copies of the whole chromosome 11. The minimal altered region of gain and/or amplification was limited to ~1.8 Mb (chr.11:69,395,184-71,209,568) and comprised mostly 11q13.3 band which contain 12 genes. Five, out of these genes (CCND1, ORAOV1, FADD, PPFIA1, CTTN) had higher expression levels in comparison to healthy controls. Apart from CCND1 gene, which has an established role in pathogenesis of head and neck cancers, CTTN, ORAOV1 and FADD genes appear to be oncogene-candidates in laryngeal cancers, while a function of PPFIA1 requires further studies.
authors: Institute of Human Genetics, Polish Academy of Sciences, Strzeszynska 32, 60-479, Poznan, Poland. maljar@man.poznan.pl
authors: Małgorzata
authors: M
authors: Jarmuz-Szymczak
authors: Kinga
authors: K
authors: Pelinska
authors: Magdalena
authors: M
authors: Kostrzewska-Poczekaj
authors: Ewa
authors: E
authors: Bembnista
authors: Maciej
authors: M
authors: Giefing
authors: Damian
authors: D
authors: Brauze
authors: Marcin
authors: M
authors: Szaumkessel
authors: Andrzej
authors: A
authors: Marszalek
authors: Joanna
authors: J
authors: Janiszewska
authors: Katarzyna
authors: K
authors: Kiwerska
authors: Anna
authors: A
authors: Bartochowska
authors: Reidar
authors: R
authors: Grenman
authors: Witold
authors: W
authors: Szyfter
authors: Krzysztof
authors: K
authors: Szyfter
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002880:Chromosomes, Human, Pair 11; D016000:Cluster Analysis; D055028:Comparative Genomic Hybridization; D005260:Female; D018628:Gene Dosage; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D015321:Gene Rearrangement; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007822:Laryngeal Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged
references: Clin Cancer Res. 2000 Aug;6(8):3177-82
references: 10955801
references: Cancer Genet Cytogenet. 2005 Jul 1;160(1):82-8
references: 15949577
references: Carcinogenesis. 2006 Oct;27(10):2034-7
references: 16638786
references: Cancer Genet Cytogenet. 2007 May;175(1):19-25
references: 17498553
references: Eur Arch Otorhinolaryngol. 2003 Nov;260(10):549-54
references: 14551784
references: EMBO J. 1995 Jun 15;14(12):2827-38
references: 7796809
references: Genes Chromosomes Cancer. 2000 Jun;28(2):153-63
references: 10825000
references: Hum Genet. 2007 Apr;121(2):187-201
references: 17171571
references: J Cell Sci. 2009 Sep 15;122(Pt 18):3225-32
references: 19690048
references: Cancer Res. 2007 Mar 15;67(6):2552-8
references: 17363573
references: Proc Natl Acad Sci U S A. 2002 Aug 20;99(17):11369-74
references: 12172009
references: Biotechniques. 1993 Sep;15(3):532-4, 536-7
references: 7692896
references: Clin Cancer Res. 2001 Oct;7(10):3127-34
references: 11595705
references: Cytogenet Genome Res. 2006;115(2):99-106
references: 17065789
references: Oncogene. 2006 Nov 2;25(52):6997-7008
references: 16715129
references: Genes Chromosomes Cancer. 2006 Feb;45(2):118-25
references: 16235239
references: Clin Cancer Res. 1997 Sep;3(9):1609-14
references: 9815850
references: Oncogene. 2006 Mar 2;25(9):1424-33
references: 16247453
references: Nat Rev Cancer. 2011 Jan;11(1):9-22
references: 21160525
references: Am J Hum Genet. 1994 Nov;55(5):968-74
references: 7977360
references: Cancer Biomark. 2010-2011;8(1):11-9
references: 21896986
references: Clin Cancer Res. 2007 Nov 1;13(21):6257-66
references: 17975136
references: Drugs. 2008;68(12):1609-19
references: 18681486
references: Genes Chromosomes Cancer. 2010 Jan;49(1):1-8
references: 19787783
references: Genes Chromosomes Cancer. 2008 Apr;47(4):353-62
references: 18196592
references: Cancer Genet Cytogenet. 2003 Jul 15;144(2):165-74
references: 12850380
references: Genes Chromosomes Cancer. 2011 Mar;50(3):154-66
references: 21213369
references: Crit Rev Oral Biol Med. 2003;14(5):363-9
references: 14530304
references: Eur Arch Otorhinolaryngol. 2006 Jan;263(1):43-8
references: 16258756
references: J Natl Cancer Inst. 2003 Feb 5;95(3):198-205
references: 12569141
references: J Clin Virol. 2012 Feb;53(2):116-20
references: 22177275
references: Cancer Genet Cytogenet. 2008 Jul;184(1):38-43
references: 18558287
references: Clin Cancer Res. 1996 Jan;2(1):175-80
references: 9816104
references: Cancer Lett. 2006 Jan 8;231(1):94-101
references: 16051426
references: Int J Oncol. 2002 Jan;20(1):45-52
references: 11743641
references: Arch Otolaryngol Head Neck Surg. 1995 Jul;121(7):790-4
references: 7598859