WW domain containing oxidoreductase gene expression is altered in non-small cell lung cancer.
WWOX (WW domain containing oxidoreductase), a putative tumor suppressor gene that maps to 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.
Yendamuri
Sai
S
Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Kuroki
Tamotsu
T
Trapasso
Francesco
F
Henry
Adam C
AC
Dumon
Kristoffel R
KR
Huebner
Kay
K
Williams
Noel N
NN
Kaiser
Larry R
LR
Croce
Carlo M
CM
D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology / Q000235:genetics*; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics*; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor; D006801:Humans; D019656:Loss of Heterozygosity; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D010088:Oxidoreductases / Q000096:biosynthesis / Q000235:genetics*; D017354:Point Mutation; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D010088:Oxidoreductases