ID

45473

Beskrivning

Principal Investigator: Laura Pasqualucci, MD, Institute for Cancer Genetics, Columbia University, New York, NY, USA MeSH: Lymphoma, Non-Hodgkin,Lymphoma, B-Cell https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000502 Splenic Marginal Zone Lymphoma (SMZL) is a B-cell malignancy of unknown pathogenesis and thus orphan of targeted therapies. By integrating whole-exome sequencing and copy-number analysis of 8 paired tumor-normal DNAs from patients with SMZL, we show that the typical SMZL exome carries ~30 genetic alterations. Targeted resequencing of selected candidates in an extended panel of 40-117 samples revealed activating mutations of NOTCH2, a gene required for marginal-zone (MZ) development, as the most frequent and SMZL-specific lesion, accounting for approximately 20% of cases. Additional altered genes suggest that deregulation of signaling pathways normally involved in MZ development (NOTCH, NF-kappa B, and B-cell receptor) represents a critical event in SMZL pathogenesis. These findings have direct implications for the treatment of SMZL patients since drugs are available which can target NOTCH as well as other pathways deregulated in this disease.

Länk

dbGap study = phs000502

Nyckelord

Versioner (2)

1. 2022-10-31 2022-10-31 - Tabea Kampen
2. 2022-12-13 2022-12-13 - Kristina Keller

Rättsinnehavare

Laura Pasqualucci, MD, Institute for Cancer Genetics, Columbia University, New York, NY, USA

Uppladdad den

13 december 2022

DOI

För en begäran logga in.

Licens