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This Week in Cancer Cell: Mar 2, 2012

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In Cancer Cell this week, researchers at St. Jude Children's Research Hospital describe their mouse model of the most aggressive subtype of human medulloblastoma. They generated the model of MYC-subgroup medulloblastoma by transducing Trp53-null cerebellar progenitor cells with MYC. "The cardinal features of these mouse medulloblastomas closely mimic those of human MYC-subgroup tumors and significantly differ from mouse models of the Sonic-Hedgehog- and WNT-disease subgroups," the authors write. "This mouse model should significantly accelerate understanding and treatment of the most aggressive form of medulloblastoma and infers distinct roles for MYC and MYCN in tumorigenesis."

Also in Cancer Cell this week, researchers at Harvard and MD Anderson Cancer Center write that adaptive resistance to treatment in matrix-attached cancer cells is caused by the inhibition of the PI3K/mTOR pathway. "This matrix-associated resistance is mediated by drug-induced upregulation of cellular survival programs that involve both FOXO-regulated transcription and cap-independent translation," the team writes. "Bypass of this resistance mechanism through rational design of drug combinations could significantly enhance PI3K-targeted drug efficacy."

Finally in Cancer Cell this week, researchers in the US and Scotland report that activation of p53 through the inhibition of SIRT1, combined with imatinib, enhances the elimination of chronic myelogenous leukemia stem cells. SIRT1 is over-expressed in human CML stem cells and inhibition or knock down of SIRT1 increases apoptosis of these cells, the team found. Further, they write that "SIRT1 effects were enhanced in combination with the BCR-ABL TKI imatinib. SIRT1 inhibition increased p53 acetylation and transcriptional activity in CML progenitors, and the inhibitory effects of SIRT1 targeting on CML cells depended on p53 expression and acetylation."

The Scan

Self-Reported Hearing Loss in Older Adults Begins Very Early in Life, Study Says

A JAMA Otolaryngology — Head & Neck Surgery study says polygenic risk scores associated with hearing loss in older adults is also associated with hearing decline in younger groups.

Genome-Wide Analysis Sheds Light on Genetics of ADHD

A genome-wide association study meta-analysis of attention-deficit hyperactivity disorder appearing in Nature Genetics links 76 genes to risk of having the disorder.

MicroRNA Cotargeting Linked to Lupus

A mouse-based study appearing in BMC Biology implicates two microRNAs with overlapping target sites in lupus.

Enzyme Involved in Lipid Metabolism Linked to Mutational Signatures

In Nature Genetics, a Wellcome Sanger Institute-led team found that APOBEC1 may contribute to the development of the SBS2 and SBS13 mutational signatures in the small intestine.