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New guidelines aim to standardize interpretation and reporting of somatic cancer variants

Friday, December 16, 2016

This is an excerpt of an article that appeared on GenomeWeb. Read the full story here.

A team lead by the Association for Molecular Pathology has developed a set of new standards and guidelines for interpreting and reporting sequence variants in cancer that it hopes will improve genomic testing and precision care for cancer patients.

The guidelines, published in the Journal of Molecular Diagnostics today, were devised by a working group of the AMP Clinical Practice Committee that included representatives from the American College of Medical Genetics and Genomics, the American Society of Clinical Oncology, and the College of American Pathologists. According to the publication, they emulate "the expert consensus opinion of the working group members with input from the stakeholders they represent."  

In a nutshell, the guidelines propose a four-tiered system for classifying somatic sequence variants, based on their clinical significance for diagnosis, prognosis, and therapy. Tier I includes variants with the highest level of evidence, such as an associated US Food and Drug Administration-approved drug, inclusion in professional guidelines, or results from well-powered studies. Tier II contains variants with potential clinical significance, for example those associated with drugs that are FDA-approved for a different tumor type, variants associated with investigational therapies, or results from small studies or preclinical trials. Tier III variants are currently of unknown clinical significance and tier IV variants are considered benign or likely benign. The guidelines also describe a process for variant annotation, classification, and reporting and include a list of commonly used bioinformatics tools and databases.


Photo of Olivier ElementoOlivier Elemento Olivier Elemento, head of the laboratory of cancer systems biology and an associate professor at Weill Cornell Medicine, said that his laboratory had already adopted many aspects of the proposed guidelines. "It is likely that we will review our reporting strategy as a result of the publication of the guidelines but I don't anticipate any major changes," he told GenomeWeb. The new standards are similar to existing best practices, he said, and he expects that most labs will review their analytical and reporting strategies "to converge towards the proposed recommendations."

"The oncology genomic testing field has been in dire need of standardization and guidelines that focus on clinical actionability of genomic testing results," he said, and the fact that the guidelines were developed by "highly respected organizations" means they will likely have a lasting impact.

However, he said he was surprised by a lack of emphasis on open, community-driven efforts to capture and catalog context and tumor-type dependent clinical interpretations of somatic alterations, such as CIViC, Weill Cornell's Precision Medicine Knowledgebase, or the Cancer Genome Interpreter. "Categorizing variants into tiers of clinical actionability needs extensive and continuous literature curation — it is critical that such efforts be shared and ideally coordinated across institutions," he said. "Otherwise we will continue to generate broadly discordant clinical reports."

Also, some recent developments are missing from the guidelines, he said, for example how to report mutational burden and neoepitope burden, which are both highly relevant for identifying patients likely to respond to immunotherapy.