Skip to main content
Premium Trial:

Request an Annual Quote

This Week in NEJM: Oct 6, 2011


In NEJM this week, researchers from the Chronic Myeloid Disorders Working Group of the International Cancer Genome Consortium present findings from a study of somatic mutation in the SF3B1 gene in patients with myelodysplastic syndromes. The team used massively parallel sequencing technology to identify somatically acquired point mutations in the genomes of nine patients with low-grade myelodysplasia, and found 64 point mutations. Recurrent somatically acquired mutations were identified in the gene SF3B1. Follow-up studies found that 72 of 354 patients with myelodysplastic syndromes had SF3B1 mutations, with high frequency among patients whose disease was characterized by ring sideroblasts. "The observed mutations were less deleterious than was expected on the basis of chance, suggesting that the mutated protein retains structural integrity with altered function," the authors write. "Clinically, patients with SF3B1 mutations had fewer cytopenias and longer event-free survival than patients without SF3B1 mutations."

Also in NEJM this week, researchers from the Breast Cancer International Research Group present findings from a study of adjuvant trastuzumab in HER2-positive breast cancer. Trastuzumab improves survival in the adjuvant treatment of HER-positive breast cancer, although trastuzumab combined with anthracycline-based treatment regimens has been associated with cardiac toxicity, the authors write. For this study, the team randomly assigned 3,222 women with HER2-positive early-stage breast cancer to three different groups: a new non-anthracycline regimen — docetaxel and carboplatin — with trastuzumab; an anthracycline-based regimen — doxorubicin and cyclophosphamide followed by docetaxel; or the anthracycline-based regimen followed by trastuzumab. At a median follow-up of 65 months, the estimated five year disease-free survival was 75 percent for patients receiving the anthracycline treatment, 84 percent for the patients receiving anthracycline plus trastuzumab, and 81 percent for the patients receiving the non-anthracycline regimen. Estimated overall survival rates were 87 percent, 92 percent, and 91 percent, respectively. Both trastuzumab regimens were superior to the third regimen, but the rates of congestive heart failure and cardiac dysfunction were significantly lower in the non-anthracycline plus trastuzumab group. "The addition of 1 year of adjuvant trastuzumab significantly improved disease-free and overall survival among women with HER2-positive breast cancer," the authors write. "The risk–benefit ratio favored the nonanthracycline TCH regimen over AC-T plus trastuzumab, given its similar efficacy, fewer acute toxic effects, and lower risks of cardiotoxicity and leukemia."

The Scan

Long COVID-19 Susceptibility Clues Contained in Blood Plasma Proteome

A longitudinal study in eBioMedicine found weeks-long blood plasma proteome shifts after SARS-CoV-2 infection, along with proteomic signatures that appeared to coincide with long Covid risk.

Tibetan Study Finds Adaptive Variant Influencing Skin Pigmentation

With a combination of phenotyping and genetic data, researchers document at PNAS a Tibetan-enriched enhancer variant influencing melanin synthesis and ultraviolet light response.

Domestication Linked to Nervous System Genes in Inbred Mouse Strains

Researchers highlighted more than 300 positively selected genes in domesticated mice, including genes linked to nervous system function or behavior in Genome Biology.

ALS Genetic Testing May Be Informative Across Age Ranges, Study Finds

Researchers in the journal Brain identified clinically actionable variants in a significant subset of older ALS patients, prompting them to point to the potential benefits of broader test use.