Mutations in the MYB intron I regulatory sequence increase transcription in colon cancers.
Although MYB overexpression in colorectal cancer (CRC) is known to be a prognostic indicator for poor survival, the basis for this overexpression is unclear. Among multiple levels of MYB regulation, the most dynamic is the control of transcriptional elongation by sequences within intron 1. The authors have proposed that this regulatory sequence is transcribed into an RNA stem-loop and 19-residue polyuridine tract, and is subject to mutation in CRC. When this region was examined in colorectal and breast carcinoma cell lines and tissues, the authors found frequent mutations only in CRC. It was determined that these mutations allowed increased transcription compared with the wild type sequence. These data suggest that this MYB regulatory region within intron 1 is subject to mutations in CRC but not breast cancer, perhaps consistent with the mutagenic insult that occurs within the colon and not mammary tissue. In CRC, these mutations may contribute to MYB overexpression, highlighting the importance of noncoding sequences in the regulation of key cancer genes.
Hugo
Honor
H
Peter MacCallum Cancer Center, East Melbourne and Department of Pathology, The University of Melbourne, Australia.
Cures
Alina
A
Suraweera
Nirosha
N
Drabsch
Yvette
Y
Purcell
Damian
D
Mantamadiotis
Theo
T
Phillips
Wayne
W
Dobrovic
Alex
A
Zupi
Gabriella
G
Gonda
Thomas J
TJ
Iacopetta
Barry
B
Ramsay
Robert G
RG
D020413:3' Untranslated Regions / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D004260:DNA Repair / Q000235:genetics; D016762:Genes, fos; D020570:Genes, myb; D006801:Humans; D007438:Introns; D018895:Microsatellite Repeats; D009154:Mutation; D009690:Nucleic Acid Conformation; D011071:Poly T / Q000235:genetics; D018807:Polymorphism, Single-Stranded Conformational; D050436:Regulatory Elements, Transcriptional / Q000235:genetics*; D014158:Transcription, Genetic
D020413:3' Untranslated Regions; D011071:Poly T