The FHIT gene 3p14.2 is abnormal in lung cancer.
To determine the role of the FHIT gene, which encompasses the fragile site at 3p14.2, we analyzed 59 tumors of the small cell and non-small cell type by reverse transcription of FHIT mRNA, followed by PCR amplification and sequencing of products. Allelic losses affecting the gene were evaluated by microsatellite polymorphism analysis and genomic alterations by hybridization using cDNA and genomic probes. Small cell lung tumors (80%) and non-small cell lung cancers (40%) showed abnormalities in RNA transcripts of FHIT, and 76% of the tumors exhibited loss of FHIT alleles. Abnormal lung tumor transcripts lack two or more exons of the FHIT gene. Small cell lung cancer tumors and cell lines were analyzed by Southern blotting and showed rearranged BamHI fragments. These data suggest a critical role of the FHIT gene in lung carcinogenesis.
Sozzi
G
G
Kimmel Cancer Center, Jefferson Medical College, Philadelphia, Pennsylvania 19107, USA.
Veronese
M L
ML
Negrini
M
M
Baffa
R
R
Cotticelli
M G
MG
Inoue
H
H
Tornielli
S
S
Pilotti
S
S
De Gregorio
L
L
Pastorino
U
U
Pierotti
M A
MA
Ohta
M
M
Huebner
K
K
Croce
C M
CM
D000595:Amino Acid Sequence; D001483:Base Sequence; D015139:Blotting, Southern; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D018288:Carcinoma, Small Cell / Q000235:genetics*; D002869:Chromosome Aberrations; D025063:Chromosome Disorders; D043283:Chromosome Fragile Sites; D002873:Chromosome Fragility; D002893:Chromosomes, Human, Pair 3; D018076:DNA, Complementary / Q000235:genetics; D004276:DNA, Satellite / Q000235:genetics; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006579:Heterozygote; D006639:Histidine / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
D018076:DNA, Complementary; D004276:DNA, Satellite; D006639:Histidine