3'-UTR poly(T/U) repeat of EWSR1 is altered in microsatellite unstable colorectal cancer with nearly perfect sensitivity.
Approximately 15% of colorectal cancers exhibit instability of short nucleotide repeat regions, microsatellites. These tumors display a unique clinicopathologic profile and the microsatellite instability status is increasingly used to guide clinical management as it is known to predict better prognosis as well as resistance to certain chemotherapeutics. A panel of five repeats determined by the National Cancer Institute, the Bethesda panel, is currently the standard for determining the microsatellite instability status in colorectal cancer. Recently, a quasimonomorphic mononucleotide repeat 16T/U at the 3' untranslated region of the Ewing sarcoma breakpoint region 1 gene was reported to show perfect sensitivity and specificity in detecting mismatch repair deficient colorectal, endometrial, and gastric cancers in two independent populations. To confirm this finding, we replicated the analysis in 213 microsatellite unstable colorectal cancers from two independent populations, 148 microsatellite stable colorectal cancers, and the respective normal samples by PCR and fragment analysis. The repeat showed nearly perfect sensitivity for microsatellite unstable colorectal cancer as it was altered in 212 of the 213 microsatellite unstable (99.5%) and none of the microsatellite stable colorectal tumors. This repeat thus represents the first potential single marker for detecting microsatellite instability.
Medicum/Department of Medical and Clinical Genetics, University of Helsinki, 00014, Helsinki, Finland, johanna.kondelin@helsinki.fi.
Johanna
J
Kondelin
Sari
S
Tuupanen
Alexandra E
AE
Gylfe
Mervi
M
Aavikko
Laura
L
Renkonen-Sinisalo
Heikki
H
Järvinen
Jan
J
Böhm
Jukka-Pekka
JP
Mecklin
Claus L
CL
Andersen
Pia
P
Vahteristo
Esa
E
Pitkänen
Lauri A
LA
Aaltonen
D020413:3' Untranslated Regions; D002148:Calmodulin-Binding Proteins / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics*; D003718:Denmark; D005387:Finland; D006801:Humans; D053842:Microsatellite Instability; D011131:Polyribonucleotides / Q000235:genetics; D034802:RNA-Binding Protein EWS; D016601:RNA-Binding Proteins / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid
D020413:3' Untranslated Regions; D002148:Calmodulin-Binding Proteins; C500986:EWSR1 protein, human; D011131:Polyribonucleotides; D034802:RNA-Binding Protein EWS; D016601:RNA-Binding Proteins