WWOX: A candidate tumor suppressor gene involved in multiple tumor types

We previously reported the construction of a P1-derived artificial chromoso me (PAC) contig encompassing a set of homozygous deletions of chromosome 16 q23-24.1 found in primary ovarian tumor material and several tumor cell lin es. Using these PAC clones in a cDNA selection experiment, we have isolated a Sau3A fragment homologous to the WWOX transcript (GenBank accession no. AF211943) from normal human ovarian surface epithelial (HOSE) cells. We dem onstrate the homozygous deletion of WWOX exons from ovarian cancer cells an d three different tumor cell lines. We also identify an internally deleted WWOX transcript from a further primary ovarian tumor. In three of these sam ples the deletions result in frameshifts, and in each case the resulting WW OX transcripts lack part, or all, of the short chain dehydrogenase domain a nd the putative mitochondrial localization signal. Sequencing revealed seve ral missense polymorphisms in tumor cell lines and identified a high level of single nucleotide polymorphism (SNP) within the WWOX gene. This evidence strengthens the case for WWOX as a tumor suppressor gene in ovarian cancer and other tumor types.