Altered structure and expression of the human retinoblastoma susceptibility gene in small cell lung cancer.
Karyotypic and molecular genetic evidence has indicated that deletion or rearrangement of both chromosomes 3 and 13 may be important in the pathology of human small cell lung cancer (SCLC). The retinoblastoma susceptibility gene, RB, on chromosome 13 band q14, has previously been shown to be altered in SCLC [J. W. Harbour et al., Science (Wash. DC), 241: 353-357, 1988; J. Yokota et al., Oncogene, 3: 471-475, 1988]. Our studies of 26 SCLC tumor and normal DNA samples indicate that 6 of 6 patients whose normal cell DNA was heterozygous for an RB restriction fragment length polymorphism have lost one of the two alleles in their tumor DNA. Consistent with other studies, we find 2 of 26 tumors with homozygous deletions within the RB gene. Of 13 SCLC cell lines examined, only 3 expressed greater than trace amounts of RB mRNA. RB protein was detected in 2 of 14 SCLC cell lines examined, unlike the results of Yokota et al. (Oncogene, 3: 471-475, 1988) which showed no RB protein in any of the 9 cell lines they examined. Only unphosphorylated RB protein was detected in SCLC cell line H209, suggesting that the RB protein may be inactivated by a novel mechanism in this cell line. These data suggest that inactivation of the RB gene is a frequent if not universal event in SCLC.
Hensel
C H
CH
Department of Cellular and Structural Biology, University of Texas Health Sciences Center, San Antonio 78284.
Hsieh
C L
CL
Gazdar
A F
AF
Johnson
B E
BE
Sakaguchi
A Y
AY
Naylor
S L
SL
Lee
W H
WH
Lee
E Y
EY
D000483:Alleles; D015153:Blotting, Western; D018288:Carcinoma, Small Cell / Q000235:genetics*; D002872:Chromosome Deletion; D002882:Chromosomes, Human, Pair 13; D015870:Gene Expression; D015321:Gene Rearrangement; D052138:Genes, Neoplasm; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D016160:Retinoblastoma Protein; D014407:Tumor Cells, Cultured
D010750:Phosphoproteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016160:Retinoblastoma Protein