MUTATIONAL ANALYSIS OF THE TRANSFORMING-GROWTH-FACTOR-BETA RECEPTOR-TYPE-II GENE IN HUMAN OVARIAN-CARCINOMA

In the present study, we evaluated a series of sporadic ovarian carcin omas for mutations within the entire coding region of T beta R-II, Usi ng reverse transcription-PCR and ''Cold'' single-strand conformational polymorphism analysis, 6 of 24 samples (25%) were found to contain co de-altering mutations in T beta R-II: (a) four mutations resulting in amino acid substitutions in the highly conserved serine/threonine kina se domain; (b) one mutation resulting in a conservative amino acid cha nge in the transmembrane domain; and (c) a I-bp insertion in the polya denylic 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 T beta R-II mutations in primary hum an ovarian carcinomas. Immunohistochemical analysis demonstrated a los s of expression of T beta R-II in 5 of 22 available tumors (23%; 4 of which also had mutations in the coding region) and decreased expressio n of T beta R-II in 10 of 22 available tumors (41%; 1 of which had a m utation in the coding region), Thus, the loss or decreased expression of TPR-ZI seems to be a common event in sporadic ovarian carcinomas, a nd mutational inactivation, due to either frameshift mutations in the polyadenylic acid microsatellite region or point mutations in conserve d functional domains, is one mechanism by which this occurs.