CARIS SCIENTIFIC ADVANCES

Phil Stafford
VP, Bioinformatics

Caris Neuropathology: Molecular Diagnostics for Today, Research Advancements for Tomorrow

The World Health Organization (WHO) recently published its fifth edition of the Classification of Tumours of the Central Nervous System (CNS5). The new edition brings about several changes to CNS tumor classifications, tumor grading and even introduces newly recognized tumor types. CNS5 emphasizes the importance of molecular diagnostics and builds upon those updates from the 2016 revised 4th edition and the interval publications of the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy (cIMPACT). With the advancement of molecular diagnostics, those CNS neoplasms with previously uncategorizable histologic patterns, marked histologic overlap, or vague immunohistochemical reactivity, now have a better chance at definitive diagnosis.

At Caris life Sciences, our state-of-the-art technology allows maximum data extraction from each CNS sample. For every molecularly profiled patient, all 22,000 genes are sequenced across both whole exome (DNA) and whole transcriptome sequencing (RNA), generating a comprehensive and detailed molecular signature. Our platform identifies the most important alterations in IDH1/2, TERT promoter, ATRX, TP53, BRAF, EGFR, CDKN2A/B, and more. The Additional Results portion of the final report also includes 1p/19q co-deletion status as well an eKaryotype which offers the ability to grossly visualize chromosomal alterations, including full gain of chromosome 7 and full loss of chromosome 10 (+7/-10).  MGMT-methylation status is performed inhouse using pyrosequencing, eliminating the need for additional send-out testing or expenditure of tissue. Ordering physicians and oncologists can be confident that the sequencing done at Caris and the results reported sufficiently fulfill those diagnostic requirements set by the WHO CNS5 for molecularly defined entities.

In addition to providing the most up-to-date diagnostic molecular data, therapy associations and clinical trial information for today’s patients, Caris’ Precision Oncology Alliance (POA) concurrently uses the sequenced molecular data to focus on research for tomorrow’s patients. The POA is the leading cancer research enterprise in the world, collaborating with physician and clinical researchers in all settings, to better understand the etiology, molecular footprint and potential targeted therapies for CNS neoplasms. Therapeutics for patients with CNS neoplasms are markedly limited, and to-date no curative options exist. Given the complex nature and sensitive territorial landscape of the brain and spinal cord advancements in the understanding of these neoplasms, identifiable driver mutations and promising therapeutic options are far overdue.

As a neuropathologist, my most important role is to be a stewardess of patient’s tissue, prioritizing the initial diagnosis for present day therapy. However, I also have an ethical and moral duty to support the advancement of the literature in this space to help better understand what causes and drives these deadly diseases for future patients. As a Caris pathologist, I am honored and humbled to be a part of a company that not only provides up-to-date molecular diagnostics, but also one that helps clinicians and researchers navigate, advance and potentially reinvent the future of CNS cancer care for tomorrow’s patients.