Spatial heterogeneity of follicular lymphoma
Follicular lymphoma (FL) is an incurable B cell malignancy characterized by advanced stage disease and a heterogeneous clinical course. Recent genomic studies have focused on profiling “single” FL biopsies over several time-points, however, multi-site sampling in solid cancers has demonstrated profound spatial intra-tumor heterogeneity (ITH) with implications for precision medicine based initiatives. This study examined the extent of spatial heterogeneity in FL by whole exome sequencing 22 synchronously removed spatially separated biopsies from 9 patients. We observed significant differences in the extent of ITH across cases, with two distinct patterns of high and low spatial heterogeneity emerging. Site-specific alterations in genes with biological, prognostic or therapeutic relevance included, TNFRSF14, PIK3CD, TNFAIP3, PTEN, EP300 and XBP1. In depth characterization of these variants using deep-sequencing techniques confirmed their discordant nature, suggesting on-going genetic diversification driving evolution after widespread tumor dissemination. There was evidence of tumors comprising multiple competing subclones, with distinct clusters of mutations demonstrating differential expansions within spatially-separated sites. For cases where spatial tumors were examined at two time-points (FL and transformation to diffuse large B cell lymphoma (DLBCL)), the degree of heterogeneity increased with transformation. Collectively, our results demonstrate that spatial ITH is prevalent in FL. The existence of site-specific aberrations suggests that a single biopsy may not be sufficient in all patients to capture the full genomic complexity present and these spatial variations need to be considered in biomarker-led clinical studies.
- 31 samples
- DAC: EGAC00001000086
- Technology: Illumina HiSeq 2500
Data sharing policy for follicular lymphoma spatial heterogeneity project
European Genome-Phenome Archive c/o European Bioinformatics Institute Wellcome Trust Genome Campus Hinxton Cambridge CB10 1SD United Kingdom To whom it may concern, This document refers to the data set, EGAS00001002492, which has been submitted to the European Genome Archive (EGA) for the restricted access by legitimate academic institutions that have agreed to comply with the terms of a Data Access Agreement drafted by Barts Cancer Institute - Follicular Lymphoma Whole Genome Sequencing Project Data Access Committee EGAC00001000086. There are a number of steps that a researcher must take to obtain access to this data and the process is overseen by our Data Access Committee, called Barts Cancer Institute - Follicular Lymphoma Whole Genome Sequencing Project Data Access Committee, contact Prof. Jude Fitzgibbon, email j.fitzgibbon@qmul.ac.uk, or Dr. Jessica Okosun, emai j.e.okosun@qmul.ac.uk Please be advised that Dr Jun Wang, j.a.wang@qmul.ac.uk, is authorized to upload data to the EGA for archiving and distribution as part of your submission process, which will enable approved researchers to have encrypted access to the data. We can confirm that this submission is consistent with the informed consent of the participants of the study or has been granted ethical approval and is in accordance with the applicable laws and regulations. Yours Sincerely, Jude Fitzgibbon Jessica Okosun Centre for Haemato-Oncology Barts Cancer Institute - a Cancer Research UK Centre of Excellence Queen Mary, University of London John Vane Science Centre, Charterhouse Square, London EC1M 6BQ
Studies are experimental investigations of a particular phenomenon, e.g., case-control studies on a particular trait or cancer research projects reporting matching cancer normal genomes from patients.
| Study ID | Study Title | Study Type |
|---|---|---|
| EGAS00001002492 | Other |
This table displays only public information pertaining to the files in the dataset. If you wish to access this dataset, please submit a request. If you already have access to these data files, please consult the download documentation.