Transflip mutations produce deletions in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is driven by the inactivation of the tumor suppressor genes (TSGs), CDKN2A (P16) and SMAD4 (DPC4), commonly by homozygous deletions (HDs). Using a combination of high density single-nucleotide polymorphism (SNP) microarray and whole genome sequencing (WGS), we fine-mapped novel breakpoints surrounding deletions of CDKN2A and SMAD4 and characterized them by their underlying structural variants (SVs). Only one third of CDKN2A and SMAD4 deletions (6 of 18) were simple interstitial deletions, rather, the majority of deletions were caused by complex rearrangements, specifically, a translocation on one side of the TSG in combination with an inversion on the other side. We designate these as "TransFlip" mutations. Characteristics of TransFlip mutations are: (1) a propensity to target the TSGs CDKN2A and SMAD4 (P < 0.005), (2) not present in the germline of the examined samples, (3) non-recurrent breakpoints, (4) relatively small (47 bp to 3.4 kb) inversions, (5) inversions can be either telomeric or centromeric to the TSG, and (6) non-reciprocal, and non-recurrent translocations. TransFlip mutations are novel complex genomic rearrangements with unique breakpoint signatures in pancreatic cancer. We hypothesize that they are a common but poorly understood mechanism of TSG inactivation in human cancer. © 2015 Wiley Periodicals, Inc.

Tremor as a Rare Manifestation of Cefepime Neurotoxicity.

The antibiotic cefepime is a fourth-generation cephalosporin with extended-spectrum coverage against both gram-positive and negative bacteria. It is commonly used in the inpatient setting to treat community-acquired pneumonia or urinary tract infection and has side effects, including diarrhea, nausea, vomiting, pruritus, headache, and, more rarely, hypersensitivity reactions or neurotoxicity. The current report is about an 88-year-old female patient who was brought to the hospital by her daughter due to an acute change in mental status resulting from a urinary tract infection. The patient received intravenous cefepime and subsequently developed a low-frequency tremor after one day of treatment. Cefepime was discontinued with a resolution of tremor in three days. Though neurotoxicity has been documented as a serious adverse event with cefepime, tremor is not one of the known neurotoxic manifestations. This patient is the first reported to develop a tremor as a neurotoxic side effect from taking cefepime. Healthcare providers should be aware of this potential side effect and may consider discontinuing treatment with cefepime if their patient develops a new tremor within days of initiating treatment.