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Genetic analysis of multiple sporadic colon carcinomas from a single patient.

Abstract
At least two separate genetic pathways of carcinogenesis in sporadic colon cancer involving the accumulation of mutations at various genetic loci have been described. About 15% of sporadic colorectal carcinomas arise via a mechanism associated with microsatellite instability (MSI) and mutations in transforming growth factor beta receptor II (TGFbetaRII), insulin-like growth factor II receptor (IGFIIR) and BAX, whilst the remaining 85% are associated with aneuploidy and gross chromosomal rearrangements. An 81-year-old woman had a sigmoid colon carcinoma resected and 18 months later developed two additional carcinomas of the caecum and transverse colon. To investigate whether there was a common genetic mechanism of carcinogenesis for the three lesions, MSI status was assessed, TGFbetaRII, IGFIIR and BAX were analysed for mutations and protein expression of transforming growth factor beta1 (TGFbeta1) and p53 were studied using immunohistochemistry. The caecal and transverse colonic carcinomas were both MSI positive but different mutations were identified in each lesion. No genetic abnormalities were identified in the sigmoid colonic carcinoma. This suggests that each carcinoma arose via a separate genetic mechanism of carcinogenesis.
AuthorsR A Barnetson, P Symons, B G Robinson, M Schnitzler
JournalInternational journal of colorectal disease (Int J Colorectal Dis) Vol. 15 Issue 2 Pg. 83-6 (Apr 2000) ISSN: 0179-1958 [Print] Germany
PMID10855548 (Publication Type: Case Reports, Journal Article)
Chemical References
  • BAX protein, human
  • Growth Substances
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Receptor, IGF Type 2
  • Receptors, Transforming Growth Factor beta
  • Transforming Growth Factor beta
  • bcl-2-Associated X Protein
  • Protein Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type II
Topics
  • Adenocarcinoma (chemistry, genetics)
  • Aged
  • Aged, 80 and over
  • Colon (chemistry, pathology)
  • Colonic Neoplasms (chemistry, genetics)
  • DNA Mutational Analysis
  • Female
  • Genes, p53
  • Growth Substances (physiology)
  • Humans
  • Microsatellite Repeats (genetics)
  • Mutation
  • Neoplasms, Multiple Primary (chemistry, genetics)
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins (genetics)
  • Proto-Oncogene Proteins c-bcl-2
  • Receptor, IGF Type 2 (genetics)
  • Receptor, Transforming Growth Factor-beta Type II
  • Receptors, Transforming Growth Factor beta (genetics)
  • Transforming Growth Factor beta (analysis)
  • bcl-2-Associated X Protein

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