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[Cancer Research 63, 878-881, February 15, 2003]
© 2003 American Association for Cancer Research

Molecular Biology and Genetics

WW Domain Containing Oxidoreductase Gene Expression Is Altered in Non-Small Cell Lung Cancer1

Sai Yendamuri2, Tamotsu Kuroki2, Francesco Trapasso, Adam C. Henry, Kristoffel R. Dumon, Kay Huebner, Noel N. Williams, Larry R. Kaiser and Carlo M. Croce3

Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107 [S. Y., T. K., F. T., K. H., C. M. C.], and Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania 19104 [A. C. H., K. R. D., N. N. W., L. R. K.]

WWOX (WW domain containing oxidoreductase), a putative tumor suppressor gene that mapsto the common fragile site FRA16D on chromosome 16q23.3-24.1, is altered in breast, esophageal, and ovarian cancer. Because the FRA3B/FHIT locus at 3p14.2 is a preferential target for genetic changes caused by tobacco smoke, we intended to evaluate the status of the FRA16D/WWOX gene in non-small cell lung cancer; we have analyzed 27 paired normal and tumor lung tissues and 8 lung cancer cell lines for WWOX alterations by reverse transcriptase-PCR, loss of heterozygosity, and mutation analysis. Transcripts missing WWOX exons were detected in 7 primary tumors (7 of 27; 25.9%) and 5 of 8 cell lines. In addition, loss of heterozygosity at the WWOX locus was observed in 10 primary tumors (10 of 27; 37.0%). We conclude that WWOX alterations occur in a significant fraction of lung cancers and may contribute to the pathogenesis of non-small cell lung cancer.




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