'Cut from the same cloth': Shared microsatellite variants among cancers link to ectodermal tissues-neural tube and crest cells

Oncotarget. 2015 Sep 8;6(26):22038-47. doi: 10.18632/oncotarget.4194.

Abstract

The pluripotent cells of the embryonic ectodermal tissues are known to be a precursor for multiple tumor types. The adaptability of these cells is a trait exploited by cancer. We previously described cancer-associated microsatellite loci (CAML) shared between glioblastoma (GBM) and lower-grade gliomas. Therefore, we hypothesized that these variants, identified from germline DNA, are shared by cancers from tissues originating from ectodermal tissues: neural tube cells (NTC) and crest cells (NCC). Using exome sequencing data from four cancers with origins to NTC and NCC, a 'signature' of loci significant to each cancer (p-value ≤ 0.01) was created and compared with previously identified CAML from breast cancer. The results of this analysis show that variant loci among the cancers with tissue origins from NTC/NCC were closely linked. Signaling pathways linked to genes with non-coding CAML genotypes revealed enriched connections to hereditary, neurological, and developmental disease or disorders. Thus, variants in genes from tissues initiating from NTC/NCC, if recurrently detected, may indicate a common etiology. Additionally, CAML genotypes from non-tumor DNA may predict cancer phenotypes and are common to shared embryonic tissues of origin.

Keywords: glioma; medulloblastoma; melanoma; microsatellite; neuroblastoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • Exome*
  • Female
  • Gene Frequency
  • Genotype
  • Glioblastoma / genetics*
  • Glioblastoma / pathology*
  • Humans
  • Male
  • Microsatellite Repeats*
  • Neoplasms, Germ Cell and Embryonal / genetics*
  • Neoplasms, Germ Cell and Embryonal / pathology*
  • Neural Crest / pathology*
  • Neural Tube / pathology*
  • Signal Transduction