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Briefings in Functional Genomics and Proteomics Advance Access published online on May 24, 2007

Briefings in Functional Genomics and Proteomics, doi:10.1093/bfgp/elm007
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© Oxford University Press, 2007, All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

Molecular analysis of deletions in human chromosome 3p21 and the role of resident cancer genes in disease

Debora Angeloni

Corresponding author. Debora Angeloni. Scuola Superiore Sant’Anna and Institute of Clinical Physiology – National Research Council (IFC-CNR), Via Moruzzi, 1 - 56124 Pisa, Italy. Tel: +39 050 315-3092, Fax: +39 050 315-3327, E-mail: angeloni{at}ifc.cnr.it

Epithelial cancers inflict a heavy human and social burden. It was estimated [Tyczynski JE, Bray F, Parkin DM. Lung cancer in Europe in 2000: epidemiology, prevention, and early detection. Lancet Oncol 2003;4:45–55 (Review)] that in Europe, in the year 2000, 347 000 persons died of lung cancer alone, the deadliest cancer disease.

Loss of heterozygosity and large homozygous deletions of the human chromosome region 3p21 are especially frequent in epithelial cancers of several organs. In fact, 3p21 is a very peculiar region of the genome harbouring, tightly clustered, several types of cancer-causing genes (CCG) (Lerman MI, Minna JD. The 630 kb lung cancer homozygous deletion region on human chromosome 3p21.3: identification and evaluation of the resident candidate tumour suppressor genes. The International Lung Cancer Chromosome 3p21.3 Tumor Suppressor Gene Consortium. Cancer Res 2000;60:6116–33).

Current results show that, unlike it was thought initially, many tumour suppressor genes (TSG) are located close by even in small genomic regions. They may be involved, perhaps with varying role, in different types of tumour, and may be influenced by the genetic background of different human populations as well as by environmental pollutants (cigarette smoking, professional exposure).

This review will discuss methods of molecular analysis of genomic deletions to uncover CCG at 3p21, will summarize the present knowledge regarding the TSGs located in this region, and will describe a possible model of epithelial cancer pathogenesis.

Keywords: 3p21, cancer stem cell (CSC), epithelial cancer, haploinsufficiency, promoter hypermethylation; loss of heterozygosity (LOH), tumour suppressor gene(s) (TSG)


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