Characteristics of an ethnically diverse cohort of children with pediatric cutaneous mastocytosis: One institution's experience.

There has been limited research exploring how the demographic characteristics of children with pediatric cutaneous mastocytosis (PCM) may influence both the cutaneous and systemic symptoms. In this observational retrospective study of 51 children with PCM, we found a significantly higher rate of gastrointestinal (GI) symptoms in children of Hispanic ethnicity (4/21,19%) compared to non-Hispanics (0/30, 0%, p = 0.024).

Inactivation of the tumor suppressor WTX in a subset of pediatric tumors.

WTX is a tumor suppressor gene expressed during embryonic development and inactivated in 20-30% of cases of Wilms tumor, the most common pediatric kidney cancer. WTX has been implicated in several cellular processes including Wnt signaling, WT1 transcription, NRF2 degradation, and p53 function. Given that WTX is widely expressed during embryonic development and has been recently shown to regulate mesenchymal precursor cells in several organs, we tested for the potential involvement of WTX in a panel of pediatric tumors and adult sarcomas.

Detection of novel actionable genetic changes in salivary duct carcinoma helps direct patient treatment.

Purpose: Salivary duct carcinomas (SDC) are a rare and aggressive subtype of salivary gland cancers for which cytotoxic chemotherapy has limited efficacy. We investigated whether genotyping analysis could detect novel tumor-specific mutations that would help direct SDC patient treatment using targeted agents.

Experimental Design: We genotyped 27 SDC archival specimens from patients followed at Massachusetts General Hospital and Massachusetts Eye and Ear Infirmary (Boston, MA) between 2000 and 2011.

Apocrine-eccrine carcinomas: molecular and immunohistochemical analyses.

Apocrine-eccrine carcinomas are rare and associated with poor prognosis. Currently there is no uniform treatment guideline. Chemotherapeutic drugs that selectively target cancer-promoting pathways may complement conventional therapeutic approaches.

Activation of PI3K signaling in Merkel cell carcinoma.

Purpose: Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine tumor, often metastatic at presentation, for which current chemotherapeutic regimens are largely ineffective. As its pathogenesis is still unknown, we hypothesized that deregulation of signaling pathways commonly activated in cancer may contribute to MCC tumorigenesis and may provide insights into targeted therapy approaches for this malignancy.

Experimental Design: We retrospectively profiled 60 primary MCC samples using a SNaPshot-based tumor genotyping assay to screen for common mutations in 13 cancer genes.

Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors.

Lung cancers harboring mutations in the epidermal growth factor receptor (EGFR) respond to EGFR tyrosine kinase inhibitors, but drug resistance invariably emerges. To elucidate mechanisms of acquired drug resistance, we performed systematic genetic and histological analyses of tumor biopsies from 37 patients with drug-resistant non-small cell lung cancers (NSCLCs) carrying EGFR mutations. All drug-resistant tumors retained their original activating EGFR mutations, and some acquired known mechanisms of resistance including the EGFR T790M mutation or MET gene amplification.

A sensitive and specific diagnostic panel to distinguish diffuse astrocytoma from astrocytosis: chromosome 7 gain with mutant isocitrate dehydrogenase 1 and p53.

One of the major challenges of surgical neuropathology is the distinction of diffuse astrocytoma (World Health Organization grade II) from astrocytosis. The most commonly used ancillary tool to solve this problem is p53 immunohistochemistry (IHC), but this is neither sensitive nor specific. Isocitrate dehydrogenase 1 (IDH1) mutations arecommon in lower-grade gliomas, with most causing a specific amino acid change (R132H) that can be detected with a monoclonal antibody.