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A possible multiclonal development in human colonic carcinomas

M Ohmura1, T Hattori

  • 1Department of Pathology, Shiga University of Medical Science, Japan.

Journal of Cancer Research and Clinical Oncology
|January 1, 1995
PubMed
Summary
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Most colonic cancers originate from a single cell (monoclonally), but a small percentage arise from multiple cells (multiclonally). This study investigated K-ras mutations and DNA ploidy in early-stage colon tumors to understand tumor development.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gastroenterology

Background:

  • Understanding the cellular origin of colorectal cancer is crucial for effective treatment and prevention strategies.
  • Colorectal carcinomas exhibit diverse histological subtypes, including protruding and superficial types, which may indicate different carcinogenic pathways.
  • The K-ras gene mutation and DNA ploidy patterns are established biomarkers for assessing tumor progression and cellular origin.

Purpose of the Study:

  • To determine if all colonic tumors originate from a single transformed cell or multiple cells.
  • To compare the K-ras mutation status and DNA ploidy patterns in different sites within early-stage colonic carcinomas.
  • To investigate potential differences in the mode of carcinogenesis between protruding-type and superficial-type colonic carcinomas.

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Main Methods:

  • Analysis of K-ras mutation and DNA ploidy patterns in two distinct sites from 40 early-stage colonic carcinomas.
  • Cytofluorometrical analysis for DNA ploidy assessment.
  • Comparison of clonality between cancer and adenoma cells in "cancer in adenoma" cases.

Main Results:

  • Protruding-type carcinomas predominantly showed diploid DNA patterns (76.9%), while superficial-type carcinomas were often aneuploid (64.3%).
  • K-ras mutations were more frequent in protruding-type (42.3%) than superficial-type (21.4%) carcinomas.
  • Most tumor sites shared identical K-ras mutations and DNA ploidy patterns, suggesting monoclonal origin, though a few cases ( <5%) exhibited distinct mutations, indicating potential multiclonality.

Conclusions:

  • Superficial-type and protruding-type colonic carcinomas appear to follow different carcinogenic pathways.
  • The majority of colonic cancers arise monoclonally from a single cell.
  • A small subset of colonic cancers (<5%) may originate multiclonally from multiple transformed cells.