Cis-Regulatory Variation and Cancer

  • Nora F. Wasserman
  • Marcelo A. NobregaEmail author


In the traditional model of human disease genetics, mutations in coding regions of the genome were assumed to underlie disease phenotypes. It is only in the recent past that functional noncoding regions – such as promoters, enhancers and silencers – have been implicated in disease states. At its most basic level, cancer is a disease caused by the misexpression of genes normally responsible for regulating cell proliferation. It is therefore logical that mutations and variants within cis-regulatory elements controlling the expression of proto-oncogenes and tumor suppressor genes would underlie some tumorigenic gene expression changes. As changes in noncoding functional elements are harder to identify than alterations in protein ­coding sequences, many of the recent insights into cis-regulatory variants involved in cancer etiology have been uncovered by genome-wide association studies (GWAS), highlighting risk variants in non-genic regions. Here, we highlight examples of cancer-associated variation in promoters, enhancers, and silencers, as well as changes to the overall architecture of a gene’s regulatory landscape. These functional characterizations bring us closer to understanding the role of cis-regulatory mutations and cancer risk/progression.


Prostate cancer MSMB Thyroid cancer FOXE1 MYC 8q24 Breast cancer FGFR2 Colorectal cancer SMAD7 EIF3H Immunoglobulin Hematologic cancer TMPRSS2 ETS 



Chromosomal conformation capture


B cell CLL/lymphoma 2


CCAAT/enhancer-binding protein beta


Chromatin immunoprecipitation


Mouse embryonic day 14.5


Eukaryotic translation initiation factor 3 subunit H


Electrophoretic mobility shift assay


v-ETS erythroblastosis virus E26 oncogene homolog


Embryonic stem


ETS variant 1


Fibroblast growth factor receptor 2


Fluorescence in situ hybridization


Forkhead box E1


Green fluorescent protein


Genome-wide association studies




Kv channel interacting protein 3 calsenilin


Lymphoblastoid cell lines


Linkage disequilibrium


Microseminoprotein beta


Proto-oncogene v-myc myelocytomatosis viral oncogene homolog


RNA ligase-mediated rapid amplification of cDNA ends


Runt-related transcription factor 2


SMAD family member 7


Single nucleotide polymorphism


Transcription factor 7-like 2


Transmembrane protease serine 2


Transcriptional start site


Upstream transcription factor


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© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Department of Human GeneticsUniversity of ChicagoChicagoUSA

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