Misexpression of disrupted HMGI architectural factors activates alternative pathways of tumorigenesis

Alexei Tkachenko, Hena R. Ashar, Aurelia M. Meloni, Avery A. Sandberg, Kiran K. Chada

Research output: Contribution to journalArticlepeer-review

54 Scopus citations


Cancer arises from aberrations in the genetic mechanisms that control growth and differentiation. HMGI-C and HMGI(Y) are members of the HMGI family of architectural factors expressed in embryonic or undifferentiated cells and highly associated with transformation. Translocations of 12q13-15 in lipomas (fat cell tumors) disrupt HMGI-C and fuse its DNA-binding domains to novel transcriptional regulatory domains. This study shows that in a rare, karyotypically distinct group of human lipomas, rearrangements of 6p21-23 produce internal deletions within HMGI(Y). Activation of the rearranged alleles leads to expression of aberrant HMGI(Y) transcripts in differentiated adipocytes. A molecular analysis of these transcripts demonstrates that fusion of HMGI DNA-binding domains to putative transcriptional regulatory domains was not necessary for lipoma formation. However, such fusions may facilitate tumor development because activation of the wild-type HMGI allele, normally required for tumorigenesis, is bypassed in lipomas which express chimeric HMGI proteins. We hypothesize that HMGI misexpression in a differentiated cell is a pivotal event in benign tumorigenesis, and the molecular pathway of tumor development depends upon the precise nature of HMGI disruption.

Original languageEnglish (US)
Pages (from-to)2276-2280
Number of pages5
JournalCancer Research
Issue number11
StatePublished - Jun 1 1997

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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