Nav: Home

Follicular lymphoma: A tale of 2 cancers

December 13, 2016

Follicular lymphoma (FL), the second most common form of non-Hodgkin lymphoma, is a largely incurable disease of B cells, yet in many cases, because of its indolent nature, survival can extend to well beyond 10 years following diagnosis. Yet in a small number of cases, histological transformation - where fast-growing cells outnumber the smaller, slow-growing cells - or early progression to aggressive lymphoma occurs. The events leading to this increased and early mortality are poorly understood. In a study published in PLOS Medicine, Sohrab Shah and colleagues from the BC Cancer Agency in Vancouver, Canada, investigate the molecular events underlying transformation and progression and show that disparate evolutionary trajectories and mutational profiles drive these two distinct clinical endpoints.

Using whole genome sequencing, the authors analyse the genome sequence of tumours and matched normal specimens from 41 patients and classify them according to their clinical endpoints: 1) patients who presented with transformation, 2) patients who experienced tumor progression within 2.5 years after starting treatment, without evidence of transformation, 3) and those who had neither transformation nor progression up to 5 years post-diagnosis. In addition, the authors use targeted capture sequencing of known follicular lymphoma associated genes in a larger cohort of 277 patients to investigate discrete genetic events that drive transformation and early progression.

The authors show that tumors that progress early evolve in different ways than those that transform. Assessing mutations at two time points and following treatment they show that for tumours that transform, the cells or clones which constitute the majority of the aggressive tumour were extremely rare at diagnosis, if at all present. In contrast, for early progressive disease the clonal architecture remains similar from the time of diagnosis to relapse, indicating that the diagnostic tumour may already contain the properties that confer resistance to treatment. Analysis of the larger cohort pinpointed key genes and biological processes that were associated with transformation and progression.

These findings provide a basis for future research on prognostic assay development and potential strategies for monitoring and treatment of patients with FL.

This study was supported by a Program Project Grant from the Terry Fox Research Institute, Grant No. 1023) to SS, MM, RDG, CS and JC. We also wish to acknowledge generous long term funding support from the BC Cancer Foundation. SS is supported by a Canada Research Chair and a Michael Smith Foundation for Health Research, MSFHR scholar award. RK was supported by a Postdoctoral Trainee Fellowship Award from MSFHR. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests:

I have read the journal's policy and the authors of this manuscript have the following competing interests: SPS is a founder and shareholder of Contextual Genomics Inc., developer of clinical genomic tests for cancer.


Kridel R, Chan FC, Mottok A, Boyle M, Farinha P, Tan K, et al. (2016) Histological Transformation and Progression in Follicular Lymphoma: A Clonal Evolution Study. PLoS Med 13(12): e1002197. doi:10.1371/journal.pmed.1002197

Author Affiliations:

Centre for Lymphoid Cancer, BC Cancer Agency, Vancouver, British Columbia, Canada
Bioinformatics Graduate Program, University of British Columbia, Vancouver, British Columbia, Canada
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada
Department of Molecular Oncology, BC Cancer Agency, Vancouver, British Columbia, Canada
Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada
Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, Canada
Jewish General Hospital, Montreal, Quebec, Canada
Translational Cell and Tissue Research Lab, Department for Imaging and Pathology, University of Leuven (KU Leuven), Leuven, Belgium
Department of Pathology, Universitaire Ziekenhuizen Leuven (UZ Leuven), Leuven, Belgium
Department of Laboratory and Pathology, Mayo Clinic, Rochester, Minnesota, United States of America
Departments of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America



Related Follicular Lymphoma Articles:

The gene behind follicular lymphoma
EPFL scientists have discovered an important gene whose loss lies behind follicular lymphoma, an incurable cancer.
Hodgkin lymphoma survivors at high risk of second cancers
Patients who are cured of Hodgkin lymphoma are at a high risk of developing a second type of cancer, particularly if they have a family history of the disease, a major new study reports.
Follicular lymphoma: A tale of 2 cancers
Many people survive well beyond 10 years following diagnosis of follicular lymphoma.
$2.5 million boost for lymphoma research through Tanoto Foundation
The SingHealth Duke-NUS Academic Medical Centre announced today that a S$2.5 million Tanoto Foundation Professorship in Medical Oncology has been conferred to Assoc Prof Lim Soon Thye, Head and Senior Consultant of the Division of Medical Oncology at the National Cancer Centre Singapore; and Assistant Dean at Duke-NUS Medical School.
Lymphoma overrides a key protein's quadruple locks
Protein chemists at Johns Hopkins report they are closer to explaining why certain blood cancers are able to crack a molecular security system and run rampant.
More Follicular Lymphoma News and Follicular Lymphoma Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Teaching For Better Humans
More than test scores or good grades — what do kids need to prepare them for the future? This hour, guest host Manoush Zomorodi and TED speakers explore how to help children grow into better humans, in and out of the classroom. Guests include educators Olympia Della Flora and Liz Kleinrock, psychologist Thomas Curran, and writer Jacqueline Woodson.
Now Playing: Science for the People

#535 Superior
Apologies for the delay getting this week's episode out! A technical glitch slowed us down, but all is once again well. This week, we look at the often troubling intertwining of science and race: its long history, its ability to persist even during periods of disrepute, and the current forms it takes as it resurfaces, leveraging the internet and nationalism to buoy itself. We speak with Angela Saini, independent journalist and author of the new book "Superior: The Return of Race Science", about where race science went and how it's coming back.