Harnessing the power of genomic sequencing augments diagnosis and treatment of lymphoid cancer

February 8, 2018, Elsevier

A new study published in The Journal of Molecular Diagnostics has established that hybrid-capture sequencing is the method of choice for sequencing "actionable" gene mutations across the most common forms of lymphoid cancer. Due to its applicability in routinely acquired formalin-fixed, paraffin-embedded tissues, this assay can be implemented by clinical laboratories into routine diagnostic workflows. It reliably identifies potentially actionable gene mutations in 91percent of patients. This assay will bring the benefits of precision diagnosis and individualized therapy to patients with lymphoid cancer.

"To realize the benefits of the most recent progress in genomics, clinical implementation of precision medicine approaches is needed in the form of novel biomarker assays. Fully implemented targeted sequencing-based assays in routine diagnostic pathology laboratories are currently lacking in lymphoid cancer care," explained Christian Steidl, MD, Senior Scientist at the BC Cancer and Associate Professor in the Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada. "Our findings demonstrate the feasibility and outline the clinical utility of integrating a lymphoma-specific pipeline into personalized cancer care."

Lymphoid cancers include diffuse large B-cell lymphomas (DLBCL), follicular lymphoma (FL), and chronic lymphocytic leukemia (CLL), which were the focus of the present study. In recent years, several sequencing-based assays have been developed, but their clinical applicability and utility for patients with specific mutations still needs to be shown. Actionable gene mutations are defined by having a reported correlation with treatment outcome, a molecular association with a particular targeted therapy, or increasing pathologic-diagnostic accuracy. Currently, most genetic mutations associated with lymphoid cancers have been identified.

"This study is remarkably comprehensive, which will help any molecular laboratory design and implement their own next-generation sequencing lymphoma panel using this work as a template," commented Robert S. Ohgami, MD, PhD, Assistant Professor of Pathology at the Stanford University Medical Center, in an accompanying editorial.

Unlike , this assay targets a select set of genes or regions with known associations with lymphoid cancer, allowing for more rapid detection of a variety of . According to this study, capture hybridization is a better method over amplicon-based sequencing, when using formalin-fixed, paraffin-embedded tissue.

Also, this assay is continuously modifiable due to its modular flexible design. The 32-gene next-generation sequencing panel described in the paper was developed with input from a group of six specialists who kept updating it based on the latest available information. "This allows for continuous integration of additional gene features as our knowledge base improves," added Dr. Steidl.

The investigators applied the assay to tissues from 219 patients with lymphoid cancers (114 FL, 76 DLBCL, and 29 CLL) who were treated in British Columbia, Canada, between 2013 and 2016. At least one actionable mutation was found in 91 percent of the tumors. The assay revealed cancer subtype-specific mutational profiles that were highly similar to published mutational profiles for all three types of lymphoid cancer. The assay was also found to have 93 percent concordance with whole-genome sequencing.

"Our developed assay harnesses the power of modern sequencing for clinical diagnostics purposes and potentially better deployment of novel treatments in lymphoid cancers. We believe our study will help establish evidence-based approaches to decision making in lymphoid cancer care. The next steps are to implement sequencing-based biomarker assays, such as reported in our study, in accredited pathology laboratories. Toward the goal of biomarker-driven clinical decision making, testing of potentially predictive biomarker assays is needed alongside clinical trials investigating novel cancer therapeutics," noted Dr. Steidl.

Explore further: CHLA launches OncoKids - a comprehensive DNA and RNA pediatric cancer panel

More information: "Assessment of Capture and Amplicon-based Approaches for the Development of a Targeted Next-generation Sequencing Pipeline to Personalize Lymphoma Management," Journal of Molecular Diagnostics (2018). DOI: 10.1016/j.jmoldx.2017.11.010

Related Stories

CHLA launches OncoKids - a comprehensive DNA and RNA pediatric cancer panel

June 21, 2017
Today, a team of investigators at Children's Hospital Los Angeles launched OncoKidsSM, a next-generation sequencing-based panel specifically designed for pediatric cancers. OncoKids is intended to guide the diagnosis and ...

Cancer researchers validate a clinical test for fusion genes

August 14, 2017
An assay that identifies a peculiar but important abnormality in cancer cells has been developed and validated by researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and ...

New assay shows promise to advance personalized therapy for cancer patients

February 7, 2017
One of the most promising areas of cancer research is personalized therapy using precision medicine. The National Cancer Institute's NCI-MATCH (Molecular Analysis for Therapy Choice) is a large, ongoing clinical trial that ...

New assay may boost targeted treatment of non-Hodgkin lymphoma

October 17, 2017
Diffuse large B-cell lymphoma (DLBCL) is an aggressive cancer and the most frequently diagnosed non-Hodgkin lymphoma worldwide (nearly 40% of cases). Recent advancements indicate that both the prognosis and choice of treatment ...

Universal sequencing of cancer genes ups mutation detection

September 7, 2017
(HealthDay)—Universal sequencing of a broad panel of cancer-related genes is associated with increased detection of potentially clinically significant heritable mutations, according to a study published online Sept. 5 in ...

Mayo Clinic launches 50-gene cancer panel test

April 28, 2014
Mayo Clinic announces the launch of CANCP, a new gene panel cancer test to help tailor chemotherapy to the individual patient based on the unique genomic signature of the patient's tumor. CANCP, an abbreviation for Solid ...

Recommended for you

New 'SLICE' tool can massively expand immune system's cancer-fighting repertoire

November 15, 2018
Immunotherapy can cure some cancers that until fairly recently were considered fatal. In addition to developing drugs that boost the immune system's cancer-fighting abilities, scientists are becoming expert at manipulating ...

Anti-malaria drugs have shown promise in treating cancer, and now researchers know why

November 15, 2018
Anti-malaria drugs known as chloroquines have been repurposed to treat cancer for decades, but until now no one knew exactly what the chloroquines were targeting when they attack a tumor. Now, researchers from the Abramson ...

Researchers identify a mechanism that fuels cancer cells' growth

November 14, 2018
Scientists at the UCLA Jonsson Comprehensive Cancer Center have identified sodium glucose transporter 2, or SGLT2, as a mechanism that lung cancer cells can utilize to obtain glucose, which is key to their survival and promotes ...

A new approach to detecting cancer earlier from blood tests: study

November 14, 2018
Cancer scientists led by principal investigator Dr. Daniel De Carvalho at Princess Margaret Cancer Centre have combined "liquid biopsy", epigenetic alterations and machine learning to develop a blood test to detect and classify ...

New antibody breakthrough to lead the fight against cancer

November 14, 2018
Scientists at the University of Southampton have developed a new antibody that could hold the key to unlocking cancer's defence against the body's immune system.

Photoacoustic imaging may help doctors detect ovarian tumors earlier

November 14, 2018
Ovarian cancer claims the lives of more than 14,000 in the U.S. each year, ranking fifth among cancer deaths in women. A multidisciplinary team at Washington University in St. Louis has found an innovative way to use sound ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.