Myriad Genetics Says myRisk Cancer Test Highly Accurate in Key Validation Study

Myriad Genetics, Inc.(Nasdaq: MYGN) today announced it will present data this week at the AmericanSociety of Human Genetics (ASHG) annual meeting in Boston showing that theMyriad myRisk Hereditary Cancer test meets rigorous quality standards andprovides clinical sequencing results equivalent to 99.99 percent accuracy.Myriad myRisk Hereditary Cancer is a new diagnostic test that providespatients with information about their hereditary risk for eight major cancersincluding breast, colorectal, ovarian, endometrial, pancreatic, prostate,gastric cancers and melanoma."Next-generation DNA sequencing offers the ability to test many genes at once,but it must be optimized to ensure clinical accuracy. We've invested threeyears of research to optimize our Myriad myRisk Hereditary Cancer test, andthe validation data show that Myriad myRisk Hereditary Cancer offers 99.99specificity and sensitivity which means it provides unprecedented quality andaccuracy equal to the gold standard Sanger sequencing," said Richard J.Wenstrup, M.D., chief medical officer of Myriad. "As next-generationtechnology advances, mutation classification techniques also must evolve toensure high quality data interpretation for clinical decision making. Myriadhas developed a robust variant classification program called Myriad myVision™to achieve highly accurate, clinically-actionable, genetic test results forpatients and healthcare providers."The five studies being presented at the ASHG annual meeting include:Development of a Next Generation Sequencing Panel to Assess Hereditary CancerRisk that Includes Clinical Diagnostic Analysis of the BRCA1 and BRCA2 Genes. [Roa et al., Poster: Oct. 24, 2013, 11:30 a.m. – 12:30 p.m. ET]This study validated the myRisk Hereditary Cancer test, which is a 25-genepanel that uses next generation sequencing (NGS) technology. The studycompared the myRisk Hereditary Cancer test to the gold standard Sangersequencing for evaluation of BRCA1 and BRCA2 mutations in 1,864 patientsamples. myRisk Hereditary Cancer detected 15,877 variants compared to 15,878variants using Sanger sequencing, resulting in an analytic sensitivity > 99.99percent.  These data show that a NGS gene panel designed to meet rigorousquality standards can provide clinical sequencing results that are equivalentto those obtained from Sanger DNA sequencing analysis (i.e., greatersensitivity without loss of specificity). In this validation study, Myriad'smyRisk Hereditary Cancer test was shown to be highly effective and providedhigh quality, accurate results for clinical decision-making purposes. A Clinical History Weighting Algorithm Accurately Classifies BRCA1 and BRCA2Variants. [Bowles et al., Poster: Oct. 25, 2013, 10:30 – 11:30 a.m. ET]This study evaluated a clinical history weighting algorithm designed toprovide highly accurate classifications for BRCA1 and BRCA2 variants ofuncertain significance and which is integral to Myriad's proprietary myVision™Variant Classification Program. The algorithm is based on the premise thatdisease-associated mutations will be observed more often in individuals athigh risk for carrying a mutation, as determined by personal and familyhistory.  Statistical analysis weights the family histories of each patientcarrying a variant of interest and compares those histories to controlpatients carrying variants known to be benign or deleterious. Data from morethan 400,000 patients were used to develop the algorithm, which was validatedagainst 6,000 BRCA1 and BRCA2 variants. The results showed that the clinicalhistory weighting algorithm accurately classified well-documented variantsassociated with BRCA1 and BRCA2 and allowed classification with fewerobservations than other techniques, providing timely and accurateclassifications to guide clinical care. Importantly, this clinical historyweighting algorithm facilitated the accurate reclassification of BRCA1 andBRCA2 variants of uncertain significance, which will improve the clinicalmanagement of patients at risk for hereditary cancer.Frequencies of BRCA1, BRCA2, PALB2, and CDKN2A Germline Mutations in FamilialPancreatic Cancer (FPC): A PACGENE study. [Zhen/Petersen et al., Poster: Oct.24, 2013, 10:30 – 11:30 a.m. ET]This study assessed the frequency of germline mutations in four of the genesin the myRisk Hereditary Cancer panel – BRCA1, BRCA2, PALB2, and CDKN2A – inpatients with familial pancreatic cancer. Using samples from a largepancreatic cancer registry, the DNA from 80 patients who met familialpancreatic cancer criteria was tested.  The frequencies for deleterious orsuspected deleterious mutations and variants of uncertain significance (VUS)among the patients tested totaled 13.8 percent: BRCA1 (2.9 percent), no VUS;BRCA2 (4.4 percent), no VUS; PALB2 (1.3 percent), no VUS; CDKN2A (5.2percent), 3 VUS.  These data show the genetic heterogeneity of germlinemutations in patients with familial pancreatic cancer and strongly suggestthat these patients are appropriate candidates for genetic testing using ahereditary cancer panel that tests for multiple genes to prevent amisdiagnosis.Detection of Large Rearrangements in PMS2. [Mancini-DiNardo et al., Podium:Oct. 25, 2013, 3:15 p.m. ET]This study evaluated the frequency of large rearrangements (LR) in the PMS2gene, which are associated with hereditary colon cancer.  While inactivationof PMS2 is caused largely by sequencing mutations, a significant proportion ofall PMS2 mutations have been reported to be large rearrangements. In thisstudy, the analysis of data from patients who received full gene sequencingand LR analysis of MLH1, MSH2, MSH6 and PMS2, demonstrated that deleteriousand suspected deleterious mutations in PMS2 comprise 14.3 percent of allmutations detected in these hereditary colon cancer predisposing genes(108/755). Among the PMS2 mutation-positive patients, 25 percent of themutations were LR compared with 75 percent that were sequencing mutations.This study showed that LR are a significant portion of PMS2 mutations. Sincemutations within PMS2 alone are clinically actionable, it is criticallyimportant to accurately assess patients' PMS2 large rearrangement status. Themultifaceted process used in this study provided patients with an accuratediagnosis.Clinical Presentation of Patients with Mutations in the APC Regions Associatedwith AFAP. [Kaushik et al., Poster: Oct. 25, 2013, 11:30 a.m. – 12:30 p.m. ET]This study evaluated the polyp history of patients with mutations in threeareas of the APC gene associated with Attenuated Familial AdenomatousPolyposis (AFAP) compared to mutations elsewhere in the gene. AFAP is asubtype of familial adenomatous polyposis (FAP) and people with FAP/AFAP areat increased risk of hereditary colorectal cancer.  A total of 1,534individuals with mutations in the APC genes were included in this study. APCmutations in the three gene regions associated with AFAP were identified in30.1 percent of patients. Of these, 65.7 percent developed less than 100colorectal adenomas. A total of 69.9 percent were found to carry an APCmutation in the remainder of the gene not associated with AFAP. Of these, 25percent developed less than 100 polyps. The majority of patients with an APCmutation in the three regions associated with AFAP were over the age of 40(72.7 percent), while the majority of patients with mutations elsewhere in theAPC gene were aged 20 to 40 (57.1 percent). This data showed a trend of lesssevere polyps and later age of testing among patients with a mutation in thethree main regions of APC associated with AFAP.  However, a substantial numberof patients were found to have more than 100 colorectal adenomas regardless ofthe region the mutation was found in, suggesting that there is no definitivegenotype/phenotype correlation between APC mutations and AFAP/FAP. This studysupports expanding the use of genetic testing earlier in life for patientswith AFAP.