Microsatellite instability and mutational analysis of transforming growth factor beta receptor type II gene (TGFBR2) in sporadic ovarian cancer

Aims-To investigate the possible role of mutations in the transforming grow th factor beta receptor type II gene (TGFBRII) in ovarian cancer and its re lation to microsatellite instability (MSI), 43 sporadic ovarian tumours wer e analysed for mutations over the entire coding region of the TGFBRII gene. Methods-Mutational analysis was performed using the polymerase chain reacti on (PCR), single strand conformation polymorphism (SSCP) gel analysis, and direct sequencing. MSI analysis included both mononucleotide and dinucleoti de microsatellite markers used for radiolabelling and gene scanning. Results-No pathogenic mutations were detected, although sequencing of the p olyadenine (poly A) tract in exon 3 using conventional techniques revealed a spurious frameshift mutation that was not present in the same samples ana lysed using a proofreading Taq polymerase. MSI analysis demonstrated an MSI negative phenotype in 40 of the 43 tumours. None of the three MSI positive tumours demonstrated MSI for mononucleotide markers only. Conclusions-These findings suggest that: (1) MSI (both conventional and mon onucleotide) is infrequent in ovarian cancer and (2) inactivation of the MS H2, MLH1, and MSH6 mismatch repair genes and TGFBR2 gene mutations do not p lay a major role in ovarian cancer tumorigenesis. The spurious TGFBR2 frame shift mutations detected by sequencing after conventional PCR underline the importance of confirming putative mutations in repetitive sequences by alt ernative methods.