News & Notes

High-dose vitamin D relieves joint and muscle pain for many breast cancer patients taking estrogen-lowering drugs

Antonella Rastelli and colleagues in the Oncology Division recruited 60 patients who reported pain and discomfort associated with anastrozole and randomized them to receive 50,000 units of vitamin D weekly or placebo. All patients also received the recommended daily dose of 400 units of vitamin D plus 1,000 milligrams of calcium. Patients receiving high-dose vitamin D reported significantly less musculoskeletal pain and also were less likely to experience pain that interfered with daily living. The research has been published online in Breast Cancer Research and Treatment (June 2011). | WU Record 7/26/11

Chemotherapy may influence leukemia relapse

Investigators in the Oncology Division, in collaboration with the Washington University Genome Institute, have sequenced the cancer genomes of eight patients with AML before and after relapse. Their data demonstrate that AML relapse is associated with the addition of new mutations and clonal evolution, shaped in part by the chemotherapy that the patients receive to establish and maintain remissions. The work is published in Nature 2012 Jan 11 [Epub ahead of print] | WU Record 1/11/12

Key genetic error found in family of blood cancers

Matt Walter, Tim Graubert, and co-workers have uncovered a critical mutation in some patients with myelodysplastic syndromes and have found that patients with the mutation are more likely to develop acute leukemia. The mutation occurs in the U2AF1 gene, which encodes a protein involved in RNA splicing. The work is published in Nat Genet 2011 Dec 11;44(1):53-7 | WU Record 12/13/11

Surprising pathway implicated in stuttering

Stuart Kornfeld and Wang-Sik Lee, Ph.D., in collaboration with Dennis Drayna, Ph.D., a senior investigator with the National Institute on Deafness and Other Communication Disorders, have obtained evidence that at least some persistent stuttering is caused by mutations in genes that encode a pathway for directing newly made lysosomal enzymes to the lysosomes. The work was published in J Biol Chem 2011 Nov 18;286(46):39786-93. | WU Record 11/22/11

Evolution provides clue to blood clotting

Alignment of 30 vertebrate von Willebrand factor sequences enabled Luke Dang, an undergraduate student in Evan Sadler's laboratory, to indentify 13 highly conserved histidine residues. One of these residues was shown to be a pH sensor that facilitates the assembly and packaging of VWF multimers upon arrival in the trans-Golgi. Dang et al., JBC 7/22/11 | WU Record 7/20/11

Estrogen-lowering drugs reduce mastectomy rates for breast cancer patients

In the first large trial of its kind in the United States, a group of investigators led by Matthew Ellis have shown that estrogen-lowering drugs can shrink tumors and reduce mastectomy rates for patients with stage II or III ER-positive breast cancer. Of the 159 women in the trial who were originally told they required mastectomy, slightly more than half saw sufficient tumor shrinkage after 16 weeks of aromatase inhibitor treatment to undergo breast-conserving surgery instead. JCO online 5/9/11 | WU Record 5/9/11

Decoding the genome: a powerful diagnostic tool

Two studies published in JAMA highlight the power of genome sequencing as a diagnostic tool. One study, led by John Welch, identified a cytogenetically invisible PML-RARA fusion gene in a patient with AML referred for stem cell transplantation. Whole-genome sequencing was completed in 7 weeks and changed the treatment plan for the patient. The second study, led by Dan Link, analyzed the genome of a patient with breast and ovarian cancer who developed treatment-related AML. The analysis revealed a novel germline TP53 mutation, which has important clinical implications for the patient’s 3 children. Welch et al., JAMA 4/20/11 | Link et al., JAMA 4/20/11 | Commentary, JAMA 4/20/11 | WU Record 4/19/11