Caris Life Sciences Data Highlighted During ASCO Presentation Showing Cascading Effects of Tumor Repair Gene Mutations and Tumor Cell Phenotype

IRVING, Texas, June 4, 2018 /PRNewswire/ -- Caris Life Sciences^®, a leading innovator in molecular science focused on fulfilling the promise of precision medicine, today announced the oral presentation of a study demonstrating the value of the large-scale cancer genomic database underlying the company's proprietary Caris Molecular Intelligence^® tumor profiling service to better understand the relationship of DNA repair gene mutations and their functional importance. The study was presented at the American Society of Clinical Oncology (ASCO) Annual Meeting on June 3, 2018, in Chicago.

"We know that mutations in DNA repair genes are common and important drivers of the microsatellite instability (MSI) phenotype and malignancy, and that bi-allelic mismatch repair (MMR) gene mutations are common in colorectal and endometrial cancers," said Michael Hall, M.D., M.S., associate professor, Department of Clinical Genetics, Fox Chase Cancer Center and investigator of the study. "However, we have little information regarding the frequency of bi-allelic MMR gene mutations in other cancers. Access to Caris' large tumor sample database enabled us to explore this question across many tumor types and demonstrated that the relationship between increased numbers of MMR gene mutations and total mutational burden (TMB) and MSI phenotypes are observed in other tumor types despite their less common occurrence. We hope this new information will spur additional work to better define the relationship and result in new therapeutic strategies to treat these challenging tumors."

David Spetzler, M.S., Ph.D., M.B.A., President and Chief Scientific Officer of Caris Life Sciences added, "This important study highlights the value of our Caris Molecular Intelligence tumor profiling service and its large tumor sample database. While the study showed that MMR mutations are relatively uncommon and occurred in less than two percent of the more than 24,000 tissue samples, the important finding was that the large number of samples enabled the researchers to identify these previously-undetermined relationships that could have an impact on treatment plans and patient outcomes. Oncologists are now better positioned to further evaluate these relationships with the ultimate objective of improving treatment management for these patients."

The study evaluated the relationship with the number of somatic mutations (SMs) in four mismatch repair (MMR) genes and the MSI phenotype, which is often associated with better prognosis in many cancers. A total of 24,233 tumor samples were queried for one mutation (mono-allelic) or two mutations (bi-allelic). From this large database, 470 tumors, or approximately two percent, had one or more mutations in MMR genes. Of these, 80, or less than 0.5 percent, had two MMR gene mutations. The study showed that tumors with bi-allelic MMR gene mutations were more common in younger patients (median age 57.5 years for bi-allelic vs. 63 years for mono-allelic (p = 0.003), which the authors suggested may be due to germline mutations that preceded somatic mutations.

In addition, bi-allelic MMR gene mutations were associated with high tumor mutational burden (TMB) and also with more mutations in non-MMR DNA repair genes, including those for nucleotide excision repair and homologous recombination genes such as BRCA1/2. Interestingly, high microsatellite instability (MSI) was only associated with a mono-allelic mutation in a specific MMR gene, MLH1. By tumor type, mono-allelic MMR gene mutations were common in endometrial, colorectal (CRC) and lung cancers. Nearly all biallelic MMR mutations, 98 percent, were found in Lynch Syndrome spectrum tumors, which are hereditary non-polyposis colorectal cancers and the most common hereditary CRC. The investigators concluded that the observed association of the number of MMR gene mutations and high TMB, MSI and non-MMR DNA repair gene mutations suggests cascade effects of DNA repair deficiency and reveals possible treatment targets.

Oral Presentation details
Sunday, June 3, 2018 – 9:24 a.m. CDT, Room S404
Oral Abstract Session:  Cancer Prevention, Hereditary Genetics, and Epidemiology,
Abstract Number: 1505
"Pathogenic somatic mutation (SM) of mismatch repair (MMR) genes and their association with microsatellite instability (MSI), tumor mutational load (TML), and SM in other DNA repair pathways in 24,223 tumor genomic profiles"
Presented by Joseph Nicholas Bodor, M.D., Ph.D., Fox Chase Cancer Center

About Caris Life Sciences
Caris Life Sciences^® is a leading innovator in molecular science focused on fulfilling the promise of precision medicine through quality and innovation, and the world's leading immunotherapy diagnostic expert. Caris Molecular Intelligence^®, the company's Comprehensive Genomic Profiling Plus (CGP+) molecular testing service, assesses DNA, RNA and proteins, including microsatellite instability (MSI), tumor mutational burden (TMB) and PD-L1, to reveal a molecular blueprint to guide more precise and personalized treatment decisions. Caris' profiling services are routinely covered by third-party payors, including CMS for Medicare patients. The ADAPT Biotargeting System^™, the company's revolutionary and unbiased profiling platform, is currently being utilized for drug target identification, therapeutic discovery and development, fixed tissue-based companion diagnostics, blood-based cancer screening and biomarker identification. Headquartered in Irving, Texas, Caris Life Sciences offers services throughout the U.S., Europe, Asia and other international markets. To learn more, please visit www.CarisLifeSciences.com.

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