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Normally, a protein called ARID5B squats on the enhancer and prevents it from dialing up activity of the fat-determining genes.
Caption: Fat Switch Energy-burning beige fat is made when a protein called ARID5B prevents a bit of DNA that acts as an enhancer from turning on two faraway genes (IRX3 and IRX5).
To find ARID5B variants related to ALL, the study compared the gene in 330 Hispanic children with ALL and 541 Hispanic individuals without ALL.
Although the high-risk versions of ARID5B were found in both white and Hispanic patients, those variants were 1.
Children with one high-risk version of ARID5B were up to 80 percent more likely to develop ALL than others.
Researchers also found evidence linking ARID5B variants to relapse risk in 1,605 pediatric ALL patients enrolled in COG studies.
of Gene subgroup SMGs symbol Hypermutated/ 21 PTEN microsatellite- PIK3CA unstable PIK3R1 ARID1A RPL22 KRAS ZFHX3 ARID5B CTCF CTNNB1 ATR GIGYF2 CSDE1 FGFR2 CCND1 LIMCH1 RBMX NKAP HIST1H2BD TNFAIP6 MIR1277 Copy number low/ 16 PTEN microsatellite- PIK3CA stable CTNNB1 ARID1A PIK3R1 CTCF KRAS FGFR2 CHD4 SPOP CSMD3 (b) SOX17 SGK1 BCOR MECOM METTL14 Copy number high 8 TP53 (serous-like) PIK3CA FBXW7 PPP2R1A PIK3R1 CHD4 PTEN CSMD3 (b) Molecular Gene name Somatic-mutation subgroup frequency Hypermutated/ Phosphatase and tensin homolog 87.
That is not to say that chromatin-remodeling genes and genes of the ubiquitin ligase complex are not also perturbed in the endometrioid subtype; indeed, a number of chromatin-remodeling genes, such as ARID1A, ARID5B, CTCF, and CHD4, are also causal or candidate driver genes in molecular subgroups dominated by endometrioid endometrial tumors (Table 1).
Hispanic patients were more likely than others in this study to inherit high-risk versions of the ARID5B and PIP4K2A genes, while African-American patients were less likely to have these variants.
Jude Pharmaceutical Sciences chair and the paper's senior author, estimated that individuals who inherited variations in the genes, known as ARID5B and IKZF1, were almost twice as likely to develop ALL.
The inherited variations in ARID5B might also influence patient response to chemotherapy, particularly to the drug methotrexate.
These findings may identify a new marker that could be used to help decide on doses of methotrexate in patients with varying ARID5B status.