How wild-type TP53 is inactivated in undifferentiated-type gastric carcinomas: Analyses of intratumoral heterogeneity in deletion and mutation of TP53

Akinobu Yoshimura, Hiroyuki Sugihara, Zhi Qiang Ling, Dun Fa Peng, Ken Ichi Mukaisho, Yoshihide Fujiyama, Takanori Hattori

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Objective: In undifferentiated-type gastric carcinoma (UGC), inactivation of TP53 is infrequent at early stages and comparable to tubular adenocarcinomas (TUBs) at advanced stages. To clarify how TP53 inactivation relates to histogenesis of UGCs, we examined p53 alterations in multiple samples of individual UGCs. Methods: We used 27 UGCs including 12 mixed types with minor tubular component (TC) and 16 with a layered structure (LS), a histological remnant of incipient signet ring cell carcinoma (SIG). We examined p53 expression immunohistochemically and analyzed loss of heterozygosity (LOH) with four microsatellite markers within 17p13.1 in multiple microdissected samples. DNA sequence of mutation hot spots in TP53 was determined in representative samples of each tumor. Results: In the mixed-type UGCs, 5 and 1 of the 8 tumors without LS showed global and regional loss of wild-type TP53, respectively, through mutation and LOH, and one fourth of the tumors with LS showed the regional loss. In the tumors with the mutation, the mutation pattern was identical between TC and poorly differentiated major component. Conclusion: The inactivation of wild-type TP53 is an earlier event before dedifferentiation of TUB to mixed-type UGC, but is less frequent and a later event in a subset of mixed-type UGC deriving from SIG.

Original languageEnglish (US)
Pages (from-to)40-49
Number of pages10
JournalPathobiology
Volume73
Issue number1
DOIs
StatePublished - Jun 1 2006
Externally publishedYes

Keywords

  • Deletion
  • Gastric carcinoma
  • Genetic lineage
  • Intratumoral heterogeneity
  • Loss of heterozygosity
  • Mutations
  • TP53

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'How wild-type TP53 is inactivated in undifferentiated-type gastric carcinomas: Analyses of intratumoral heterogeneity in deletion and mutation of TP53'. Together they form a unique fingerprint.

  • Cite this