A familial frontotemporal dementia associated with C9orf72 repeat expansion and dysplastic gangliocytoma

A hexanucleotide repeat expansion in the chromosome 9 open reading frame 72 gene (C9orf72) was recently identified as the most common genetic cause of frontotemporal dementia/amyotrophic lateral sclerosis. Here we describe the clinical, pathologic, and genetic features of a Finnish C9orf72 expansion carrier, who developed a dysplastic gangliocytoma (Lhermitte-Duclos disease), a rare hamartoma/overgrowth syndrome of cerebellar granule cells associated with mutations in the phosphatase and tensin homolog gene. In addition to the dysplastic gangliocytoma, the patient showed typical transactive response DNA-binding protein with M_r 43 kD (TDP-43) pathology mainly in the cortex and the substantia nigra and numerous p62-positive/TDP-43-negative inclusions in the cerebellar granule cells. His sister carried the same gene defect and showed a similar type of TDP-43/p62 pathology in her brain. Our findings confirm that the clinical and pathologic picture of C9orf72 mutation carriers is more heterogeneous than originally thought and warrants further studies on the possible involvement of phosphatase and tensin homolog gene pathway in the specific cerebellar granule cell pathology associated with C9orf72 expansion.     

Smoking as an independent risk factor for severe skin reactions due to adjuvant radiotherapy for breast cancer

Risk factors for severe acute radiation skin reactions (ARSR) have been described with conflicting results. The aim of this study was to identify risk factors for the development of severe ARSR in women undergoing adjuvant radiotherapy (RT) for breast cancer.390 women were assessed at the first and final RT sessions and at followup. ARSR were measured by the Radiation Therapy Oncology Group/The Organization for Research and Treatment of Cancer, Acute Radiation Morbidity Scoring Criteria (RTOG/EORTC scale). Patients reported symptoms using visual analogue scale (VAS). Health related quality of life was assessed by EORTC QLQ-C30 and sleep disturbances by the MOS-Sleep questionnaire. Clinical data included smoking status (carbon monoxide in expired air), body mass index (BMI) and treatment data.RT dose, ≥50 Gy (mean difference 1.9 CI: 1.0 to 3.5, p = 0.040), high BMI (mean difference 4.3 CI: 2.2 to 8.3, p < 0.001) and smoking (mean difference 2.5 CI. 1.1 to 5.7, p = 0.027) were the factors strongest related to severe ARSR. Patients' with severe ARSR reported higher levels of pain and increased sleeping problems.To stop smoking during RT is the best decision patients can make to reduce the risk for severe ARSR since smoking is an independent risk factor.     

Targeted sequencing using a 47 gene multiple myeloma mutation panel (M3P) in ‐17p high risk disease

We constructed a multiple myeloma (MM)‐specific gene panel for targeted sequencing and investigated 72 untreated high‐risk (del17p) MM patients. Mutations were identified in 78% of the patients. While the majority of studied genes were mutated at similar frequency to published literature, the prevalence of TP53 mutation was increased (28%) and no mutations were found in FAM46C. This study provides a comprehensive insight into the mutational landscape of del17p high‐risk MM. Additionally, our work demonstrates the practical use of a customized sequencing panel, as an easy, cheap and fast approach to characterize the mutational profile of MM.