Frequency of Smad gene mutations in human cancers.
Much excitement has recently been generated by the discovery of the Smad genes, encoding proteins that transduce signals from the transforming growth factor beta family of cytokines. Here, we report the completion of cloning of the six known human Smads, providing novel sequences for Smad5 and Smad6. Previously, Smad4 and Smad2 were shown to be mutated in human cancers. However, analysis of the other four Smad genes revealed no mutations in a total of 167 tumors, including those from colon, breast, lung, and pancreas. These results suggest that the various Smad genes have different functions and demonstrate that mutations in these four genes do not, in general, account for the widespread resistance to transforming growth factor beta that is found in human tumors.
Riggins
G J
GJ
The Johns Hopkins Oncology Center, Baltimore, Maryland 21231, USA.
Kinzler
K W
KW
Vogelstein
B
B
Thiagalingam
S
S
D000595:Amino Acid Sequence; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism; D005260:Female; D016147:Genes, Tumor Suppressor / Q000235:genetics / Q000502:physiology; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism; D051785:Smad Proteins; D051899:Smad2 Protein; D051900:Smad3 Protein; D051901:Smad4 Protein; D051902:Smad5 Protein; D051905:Smad6 Protein; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D010750:Phosphoproteins; C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; C497796:SMAD4 protein, human; C497797:SMAD5 protein, human; C497802:SMAD6 protein, human; D051785:Smad Proteins; D051899:Smad2 Protein; D051900:Smad3 Protein; D051901:Smad4 Protein; D051902:Smad5 Protein; D051905:Smad6 Protein; D015534:Trans-Activators