SETD2

SETD2

A gene on chromosome 3p21.31 that encodes a ubiquitously expressed histone methyltransferase that specifically methylates Lys-36 of histone H3. Lys-36 methylation is a specific tag for epigenetic transcriptional activation. SETD2 likely plays a role in chromatin structure modulation during elongation via its interaction with hyperphosphorylated POLR2A. It may also act as a promoter-binding transcription activator.
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Caris now offers custom multiplatform testing for key markers that define recently identified subtypes of RCC, such as SETD2, PBRM1, as well as immuno-modulatory proteins.
Loss of histone 3 lysine 36 trimethylation (H3K36me3), which is associated with SETD2 mutations (which also play a role in tumor suppression), was observed in 30% of ccRCC samples.
Deleterious mutations have been observed to be enriched in genes that were not previously appreciated to have a role in suppressing cancer, such as the chromatin regulators ARID 1A, PBRM1, and SETD2, thus broadening our understanding of the cellular pathways deregulated during oncogenesis.
The study points to a molecular pathway involving a gene called SETD2, which can mutate in blood cells during a critical step as DNA is being transcribed and replicated.
We identified a gene mutation involving SETD2 that contributes to the initiation and progression of leukemia by promoting the self-renewal potential of leukemia stem cells.
They discovered activation of the MLL-NRIP3 fusion leukemia started the molecular cascade that led to bi-allelic (two mutations) in the gene SETD2 - a tumor suppressor and enzyme that regulates a specific histone modification protein called H3K36me3.
During a process called transcriptional elongation, SETD2 and H3K36me3 normally mark the zone for accurate gene transcription along the DNA.
Researchers also noticed mutation of SETD2 activated two genes (MTOR and JAK-STAT) that known contributors to cancer and leukemia.
That treatment resulted in a marked decrease in cell growth, indicating that SETD2 mutations activate numerous molecular pathways to generate leukemia.