The S387Y mutations of the transforming growth factor-beta receptor type I gene is uncommon in metastases of breast cancer and other common types of adenocarcinoma.
Recently, mutations of the transforming growth factor-beta receptor type I gene have been reported to occur at high frequency in breast cancer metastases, with all mutations being an identical C to A transversion at nucleotide 1160 of the gene (T. Chen et al, Cancer Res., 58: 4805-4810, 1998). This mutation would result in a serine to tyrosine substitution at codon 387 (S387Y) and would reportedly disrupt receptor function. Because this mutation reportedly occurred at high frequency in breast cancer metastases (42%) and much less frequently in primary breast cancer tumors (6%), this would seem to represent a pivotal genetic alteration in breast cancer progression. To further investigate the possible role of this specific genetic alteration in the progression of breast cancer and other forms of adenocarcinoma, we analyzed 20 breast cancer metastases, 15 lung adenocarcinoma metastases, and 13 colorectal cancer metastases for possible mutations at this site. Using both single-strand conformation polymorphism screening and sequencing, we found no mutations of this gene in any of our samples. Our results suggest the S387Y mutation of the transforming growth factor-beta receptor type I gene is not common in these types of human cancers.
Anbazhagan
R
R
Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21224, USA.
Bornman
D M
DM
Johnston
J C
JC
Westra
W H
WH
Gabrielson
E
E
D030201:Activin Receptors, Type I; D000230:Adenocarcinoma / Q000145:classification / Q000235:genetics* / Q000556:secondary*; D019943:Amino Acid Substitution; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D009362:Neoplasm Metastasis / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D013329:Structure-Activity Relationship
D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I