Such genes help regulate cell division, and when they are missing or
inactivated by mutations, cell division runs amok, resulting in tumors.
Not exact matches
«Our new data is scientifically important because ataluren restores activity to genes
inactivated by nonsense
mutations, and as a result, it has the potential to do so much for a large number of very complex genetic disorders,» Jacobson said.
The two studies together suggest that single copies of
inactivating ANGPTL3
mutations are found in roughly one of every 250 people of European descent, whereas people with
mutations in both copies of the gene — as in the family studied
by Musunuru and colleagues — are much rarer.
Working with colleagues at St. Vincent's Hospital in Sydney, Martin identified two individuals who had the characteristics of hereditary nonpolyposis colorectal cancer, which is usually caused
by a
mutation that
inactivates one of a person's two copies of the tumor suppressor gene MLH1, but who showed no signs of
mutation.
«We can now study these different
mutations and learn how this protein works
by how it gets
inactivated,» he said.
In summary, our study demonstrates that
inactivating mutations of KDM6A, which are common in urothelial bladder carcinoma, are potentially targetable
by inhibiting EZH2.
Cantley's lab and collaborators found that large doses of vitamin C did indeed kill cultured colon cancer cells with BRAF or KRAS
mutations by raising free radical levels, which in turn
inactivate an enzyme needed to metabolize glucose, depriving the cells of energy.
To shift into red pigment production, the enzyme flavonoid 3», 5» - hydroxylase (F3» 5 «h) is functionally
inactivated in the 13 red - flowered species they examined
by mutations that abolish enzyme activity.
This is in accordance with previous reports that decitabine and 5 - azacytidine produce a marked synergistic effect in combination with suberoylanilide hydroxamic acid and romidepsin in T - lymphoma cell lines
by modulating cell cycle arrest and apoptosis.26, 27 As a mechanism of action, KMT2D
mutations of B - lymphoma cells promote malignant outgrowth
by perturbing methylation of H3K4 that affect the JAK - STAT, Toll - like receptor, or B - cell receptor pathway.28, 29 Here our study indicated that dual treatment with chidamide and decitabine enhanced the interaction of KMT2D with the transcription factor PU.1, thereby
inactivating the H3K4me - associated signaling pathway MAPK, which is constitutively activated in T - cell lymphoma.13, 30,31 The transcription factor PU.1 is involved in the development of all hematopoietic lineages32 and regulates lymphoid cell growth and transformation.33 Aberrant PU.1 expression promotes acute myeloid leukemia and is related to the pathogenesis of multiple myeloma via the MAPK pathway.34, 35 On the other hand, PU.1 is also shown to interact with chromatin remodeler and DNA methyltransferease to control hematopoiesis and suppress leukemia.36 Our data thus suggested that the combined action of chidamide and decitabine may interfere with the differentiation and / or viability of PTCL - NOS through a PU.1 - dependent gene expression program.
Studies
by ours and other groups have shown that a number of EphA2 and EphA3
mutations inactivate Eph receptor canonical signaling
by disrupting ephrin binding or kinase activity, consistent with a role of canonical signaling in tumor suppression.
Background: Familial combined hypolipidemia, a Mendelian condition characterized
by substantial reductions in all 3 major lipid fractions, is caused
by mutations that
inactivate the gene angiopoietin - like 3 (ANGPTL3).
Intriguingly, one of the most frequently altered genes, mutated exclusively
by inactivating mutation, was LYST (10 %), which may represent a novel cancer gene in chordoma.Chordoma is a rare often incurable malignant bone tumour.
In previous work on DIPG, Lewis found that
mutations can cause a histone to inhibit the enzyme PRC2, which
inactivates genes
by compacting them.
Finally, an
inactivating mutation of LARP7 has been linked to a novel form of familial Primordial Dwarfism characterized
by facial dysmorphism and intellectual disability (Alazami et al., 2012).
BRCA1 is a classical tumor suppressor and it is
inactivated only when both gene copies / alleles are mutated (one
by germ - line
mutation and the other
by somatic
mutation).