Mutational Analysis of the Transforming Growth Factor β Receptor Type II Gene in Human Ovarian Carcinoma¹ Free

In the present study, we evaluated a series of sporadic ovarian carcinomas for mutations within the entire coding region of TβR-II. Using reverse transcription-PCR and “Cold” single-strand conformational polymorphism analysis, 6 of 24 samples (25%) were found to contain code-altering mutations in TβR-II: (a) four mutations resulting in amino acid substitutions in the highly conserved serine/threonine kinase domain; (b) one mutation resulting in a conservative amino acid change in the transmembrane domain; and (c) a 1-bp insertion in the polyadenylic acid microsatellite region resulting in a reading frameshift. In addition, six cases (25%) exhibited a common bp substitution (C→T at nucleotide 1322) in both tumor and patient-matched normal tissues. This is the first report of such TβR-II mutations in primary human ovarian carcinomas. Immunohistochemical analysis demonstrated a loss of expression of TβR-II in 5 of 22 available tumors (23%; 4 of which also had mutations in the coding region) and decreased expression of TβR-II in 10 of 22 available tumors (44%; 1 of which had a mutation in the coding region). Thus, the loss or decreased expression of TβR-II seems to be a common event in sporadic ovarian carcinomas, and mutational inactivation, due to either frameshift mutations in the polyadenylic acid microsatellite region or point mutations in conserved functional domains, is one mechanism by which this occurs.