Point mutation and homozygous deletion of PTEN/MMAC1 in primary bladder cancers

Paul Cairns, Ella Evron, Kenji Okami, Naomi Halachmi, Manel Esteller, James G. Herman, Shikha Bose, Steven I. Wang, Ramon Parsons, David Sidransky

Research output: Contribution to journalArticlepeer-review

160 Scopus citations


A new tumor suppressor gene PTEN/MMAC1 was recently isolated at chromosome 10q23 and found to be inactivated by point mutation or homozygous deletion in glioma, prostate and breast cancer. PTEN/MMAC1 was also identified as the gene predisposing to Cowden disease, an autosomal dominant cancer predisposition syndrome associated with an increased risk of breast, skin and thyroid tumors and occasional cases of other cancers including bladder and renal cell carcinoma. We screened 345 urinary tract cancers by microsatellite analysis and found chromosome 10q to be deleted in 65 of 285 (23%) bladder and 15 of 60 (25%) renal cell cancers. We then screened the entire PTEN/MMAC1 coding region for mutation in 25 bladder and 15 renal cell primary tumors with deletion of chromosome 10q. Two somatic point mutations, a frameshift and a splicing variant, were found in the panel of bladder tumors while no mutation was observed in the renal cell carcinomas. To screen for homozygous deletion, we isolated two polymorphic microsatellite repeats from genomic BAC clones containing the PTEN/MMAC1 gene. Using these new informative markers, we identified apparent retention at the gene locus indicative of homozygous deletion of PTEN/MMAC1 in four of 65 bladder and 0 of 15 renal cell tumors with LOH through chromosome 10q. Identification of the second inactivation event bladder tumors with LOH of 10q implies that PTEN/MMAC1 gene is occasionally involved in bladder tumorigenesis. However, the low frequency of biallelic inactivation suggests that either PTEN/MMAC1 is inactivated by other mechanisms or it is not the only target of chromosome 10q deletion in primary bladder and renal cell cancer.

Original languageEnglish (US)
Pages (from-to)3215-3218
Number of pages4
Issue number24
StatePublished - Jun 18 1998


  • Bladder cancer
  • Chromosome 10q
  • Homozygous deletion
  • Renal cell cancer

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research


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