RGD Reference Report - Frameshift mutation of a histone methylation-related gene SETD1B and its regional heterogeneity in gastric and colorectal cancers with high microsatellite instability. - Rat Genome Database

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Frameshift mutation of a histone methylation-related gene SETD1B and its regional heterogeneity in gastric and colorectal cancers with high microsatellite instability.

Authors: Choi, Youn Jin  Oh, Hye Rim  Choi, Mi Ryoung  Gwak, Min  An, Chang Hyeok  Chung, Yeun Jun  Yoo, Nam Jin  Lee, Sug Hyung 
Citation: Choi YJ, etal., Hum Pathol. 2014 Aug;45(8):1674-81. doi: 10.1016/j.humpath.2014.04.013. Epub 2014 Apr 24.
RGD ID: 150429646
Pubmed: PMID:24925220   (View Abstract at PubMed)
DOI: DOI:10.1016/j.humpath.2014.04.013   (Journal Full-text)

Histone methyltransferase (HMT), which catalyzes a histone methylation, is frequently altered in cancers at mutation and expression levels. The aims of this study were to explore whether SETD1B, SETDB2, and SETD2, SET domain-containing HMT genes, are mutated and expressionally altered in gastric (GC) and colorectal cancers (CRC). In a public database, we found that SETD1B, SETDB2, and SETD2 had mononucleotide repeats in coding sequences that might be mutation targets in cancers with microsatellite instability (MSI). We analyzed the mutations in 76 GCs and 93 CRCs and found SETD1B (38.7% of GC and 35.6% of CRC with high MSI [MSI-H]), SETDB2 (11.1% of CRC with MSI-H), and SETD2 frameshift mutations (6.7% of CRC with MSI-H). These mutations were not found in stable MSI/low MSI. In addition, we analyzed intratumoral heterogeneity (ITH) of SETD1B mutation in 6 CRCs and found that 2 CRCs harbored regional ITH of SETD1B. We also analyzed SETD1B expression in GC and CRC by immunohistochemistry. Loss of SETD1B expression was identified in 15% to 55% of the GC and CRC with respect to the MSI status. Of note, the loss of expression was more common in those with SETD1B mutations than those with wild-type SETD1B. We identified alterations of SET domain-containing HMT at various levels (frameshift mutations, genetic ITH, and expression loss), which together might play a role in tumorigenesis of GC and CRC with MSI-H. Our data suggest that mutation analysis in multiple regions is needed for a better evaluation of mutation status in CRC with MSI-H.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
colorectal cancer  IAGP 150429646DNA:frameshift mutation:exon 3:c.4219delA (human)RGD 
colorectal cancer  ISOSETD2 (Homo sapiens)150429646; 150429646DNA:frameshift mutation:exon 3:c.4219delA (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Setd2  (SET domain containing 2, histone lysine methyltransferase)

Genes (Mus musculus)
Setd2  (SET domain containing 2)

Genes (Homo sapiens)
SETD2  (SET domain containing 2, histone lysine methyltransferase)


Additional Information