BACKGROUND & AIMS: Cell-cycle inhibitor and tumor-suppressor gene p16/MTS1 was found to be altered in a variety of human tumors. To directly investigate genetic alterations and expression of p16/MTS1 and p15/MTS2, this study surveyed pancreatic tumors. METHODS: Cell-cycle inhibitors were analyzed for genetic alterations and expression by polymerase chain reaction, DNA sequencing, reverse-transcription polymerase chain reaction, and Western blotting. RESULTS: The analysis of pancreatic adenocarcinoma (19 cell lines and 3 xenografts) for p16/MTS1 and p15/MTS2 revealed homozygous deletions in 10 of 22 cases (46%) (7 cell lines and 3 xenografts) involving both genes. We show in these 7 cell lines as well as in 3 additional cases (10 of 19[53%]) loss of p16/MTS1 transcripts and in 2 further cases (12 of 19 [63%]) mutations leading to the loss of p16 protein. The frequency of mutations in p16/MTS1 was 56% (5 of 9). In contrast to p16/MTS1, p15/MTS2 transcripts were obtained in all cases exhibiting the p15/MTS2 gene (54%). Loss of expression was not observed for p27 and p18. CONCLUSIONS: These results support that loss of p16 function could be involved in pancreatic cancer and may explain at least in part the aggressive behavior of this tumor type.
BACKGROUND & AIMS: Cell-cycle inhibitor and tumor-suppressor gene p16/MTS1 was found to be altered in a variety of humantumors. To directly investigate genetic alterations and expression of p16/MTS1 and p15/MTS2, this study surveyed pancreatic tumors. METHODS: Cell-cycle inhibitors were analyzed for genetic alterations and expression by polymerase chain reaction, DNA sequencing, reverse-transcription polymerase chain reaction, and Western blotting. RESULTS: The analysis of pancreatic adenocarcinoma (19 cell lines and 3 xenografts) for p16/MTS1 and p15/MTS2 revealed homozygous deletions in 10 of 22 cases (46%) (7 cell lines and 3 xenografts) involving both genes. We show in these 7 cell lines as well as in 3 additional cases (10 of 19[53%]) loss of p16/MTS1 transcripts and in 2 further cases (12 of 19 [63%]) mutations leading to the loss of p16 protein. The frequency of mutations in p16/MTS1 was 56% (5 of 9). In contrast to p16/MTS1, p15/MTS2 transcripts were obtained in all cases exhibiting the p15/MTS2 gene (54%). Loss of expression was not observed for p27 and p18. CONCLUSIONS: These results support that loss of p16 function could be involved in pancreatic cancer and may explain at least in part the aggressive behavior of this tumor type.
Authors: Berthold Gerdes; Annette Ramaswamy; Andreas Ziegler; Sven A Lang; Michael Kersting; Renate Baumann; Anja Wild; Roland Moll; Matthias Rothmund; Detlef K Bartsch Journal: Ann Surg Date: 2002-01 Impact factor: 12.969
Authors: M Wagner; F R Greten; C K Weber; S Koschnick; T Mattfeldt; W Deppert; H Kern; G Adler; R M Schmid Journal: Genes Dev Date: 2001-02-01 Impact factor: 11.361