Refined physical map of the human PAX2/HOX11/NFKB2 cancer gene region at 10q24 and relocalization of the HPV6AI1 viral integration site to 14q13.3-q21.1.
BACKGROUND
Chromosome band 10q24 is a gene-rich domain and host to a number of cancer, developmental, and neurological genes. Recurring translocations, deletions and mutations involving this chromosome band have been observed in different human cancers and other disease conditions, but the precise identification of breakpoint sites, and detailed characterization of the genetic basis and mechanisms which underlie many of these rearrangements has yet to be resolved. Towards this end it is vital to establish a definitive genetic map of this region, which to date has shown considerable volatility through time in published works of scientific journals, within different builds of the same international genomic database, and across the differently constructed databases.


RESULTS
Using a combination of chromosome and interphase fluorescent in situ hybridization (FISH), BAC end-sequencing and genomic database analysis we present a physical map showing that the order and chromosomal orientation of selected genes within 10q24 is CEN-CYP2C9-PAX2-HOX11-NFKB2-TEL. Our analysis has resolved the orientation of an otherwise dynamically evolving assembly of larger contigs upstream of this region, and in so doing verifies the order and orientation of a further 9 cancer-related genes and GOT1. This study further shows that the previously reported human papillomavirus type 6a DNA integration site HPV6AI1 does not map to 10q24, but that it maps at the interface of chromosome bands 14q13.3-q21.1.


CONCLUSIONS
This revised map will allow more precise localization of chromosome rearrangements involving chromosome band 10q24, and will serve as a useful baseline to better understand the molecular aetiology of chromosomal instability in this region. In particular, the relocation of HPV6AI1 is important to report because this HPV6a integration site, originally isolated from a tonsillar carcinoma, was shown to be rearranged in other HPV6a-related malignancies, including 2 of 25 genital condylomas, and 2 of 7 head and neck tumors tested. Our finding shifts the focus of this genomic interest from 10q24 to the chromosome 14 site.
Gough
Sheryl M
SM
Cancer Genetics Research Group, Christchurch School of Medicine & Health Sciences, Christchurch, New Zealand. sheryl.gough@chmeds.ac.nz
McDonald
Margaret
M
Chen
Xiao-Ning
XN
Korenberg
Julie R
JR
Neri
Antonino
A
Kahn
Tomas
T
Eccles
Michael R
MR
Morris
Christine M
CM
D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D004279:DNA, Viral / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D023061:Gene Order / Q000235:genetics; D052138:Genes, Neoplasm / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D016328:NF-kappa B / Q000235:genetics*; D052003:NF-kappa B p52 Subunit; D015513:Oncogene Proteins / Q000235:genetics*; D051762:PAX2 Transcription Factor; D027383:Papillomaviridae / Q000235:genetics*; D030361:Papillomavirus Infections / Q000235:genetics; D020161:Physical Chromosome Mapping / Q000379:methods*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D017422:Sequence Analysis, DNA / Q000379:methods; D014157:Transcription Factors / Q000235:genetics*; D014412:Tumor Virus Infections / Q000235:genetics; D016662:Virus Integration / Q000235:genetics*
D004279:DNA, Viral; D004268:DNA-Binding Proteins; D005819:Genetic Markers; D018398:Homeodomain Proteins; D016328:NF-kappa B; D052003:NF-kappa B p52 Subunit; D015513:Oncogene Proteins; D051762:PAX2 Transcription Factor; C497318:PAX2 protein, human; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; C071250:TLX1 protein, human