The presence of K-ras point mutations defines a subgroup of patients with lung adenocarcinoma in whom the prognosis is very poor and disease-free survival is not usually long despite radical resection and a small tumor load.
Follicular lymphoma (FL) is typically a slow growing cancer that can be effectively treated. Some patients undergo transformation to diffuse large B cell lymphoma (DLBCL), which is frequently resistant to chemotherapy and is generally fatal. Targeted sequencing of DNA and RNA was applied to identify mutations and transcriptional changes that accompanied transformation in a cohort of 16 patients, including 14 with paired samples. In most cases we found mutations that were specific to the FL clone dominant at diagnosis, supporting the view that DLBCL does not develop directly from FL, but from an ancestral progenitor. We identified frequent mutations in TP53, cell cycle regulators (cyclins and cyclin-dependent kinases) and the PI3K pathway, as well as recurrent somatic copy number variants (SCNVs) on chromosome 3, 7 and 17p associated with transformation.
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