Parkway, CA, United States
Parkway, CA, United States

Time filter

Source Type

Phin S.,ResearchDx | Moore M.W.,ResearchDx | Cotter P.D.,ResearchDx | Cotter P.D.,University of California at San Francisco
Frontiers in Oncology | Year: 2013

The phosphatase and tensin homolog gene (PTEN) on chromosome 10q23.3 is a negative regulator of the PIK3/Akt survival pathway and is the most frequently deleted tumor suppressor gene in prostate cancer. Monoallelic loss of PTEN is present in up to 60% of localized prostate cancers and complete loss of PTEN in prostate cancer is linked to metastasis and androgen-independent progression. Studies on the genomic status of PTEN in prostate cancer initially used a two-color fluorescence in situ hybridization (FISH) assay for PTEN copy number detection in formalin fixed paraffin embedded tissue preparations. More recently, a four-color FISH assay containing two additional control probes flanking the PTEN locus with a lower false-positive rate was reported. Combined with the detection of other critical genomic biomarkers for prostate cancer such as ERG, androgen receptor, and MYC, the evaluation of PTEN genomic status has proven to be invaluable for patient stratification and management. Although less frequent than allelic deletions, point mutations in the gene and epigenetic silencing are also known to contribute to loss of PTEN function, and ultimately to prostate cancer initiation. Overall, it is clear that PTEN is a powerful biomarker for prostate cancer. Used as a companion diagnostic for emerging therapeutic drugs, FISH analysis of PTEN is promisingly moving human prostate cancer closer to more effective cancer management and therapies. © 2013 Phin, Moore and Cotter.


News Article | December 1, 2016
Site: www.prweb.com

ResearchDx/PacificDx announced today that it will share findings demonstrating the value of DNA microarray comparative genomic hybridization (array CGH) for HER2 genomic subtyping in breast cancer patients at this year’s San Antonio Breast Cancer Symposium. Using molecular test results from tumors with previously documented positive, negative, and equivocal HER2 status, the abstract accepted for presentation will show how high-resolution DNA-based testing can precisely determine a patient’s HER2 status allowing physicians to make decisions about anti-HER2 therapies based on the HER2 genomic subtype of the tumor. Using molecular data generated from tumor-targeted DNA extractions in their CAP/CLIA certified laboratory, the ResearchDx/PacificDx team focused on the patient subset with tumors that had been called “equivocal” for HER2 gene status. The HER2 gene is a known driver of breast cancer and definitive documentation of the HER2 status in a patient's tumor is critically important for predicting response to targeted anti-HER2 therapies. High-resolution HER2 testing accurately classified the HER2 status in 100% of the tumors and defined the HER2-Low genomic subtype most often called “equivocal” by standard testing methods. This subcategory is characterized at the protein level by low expression of the HER2 protein and no amplification of the HER2 gene on chromosome 17. Response to Herceptin in HER2-Low patients is being studied by the NSABP-B47 clinical trial (hyperlink to trial http://www.nsabp.pitt.edu/B-47.asp). “The equivocal HER2 category has become so accepted in breast cancer, people may not recognize the biological reality that this is not a genomic subtype,” said ResearchDx/PacificDx Chief Medical Officer Dr. Shelly Gunn. “In the era of precision medicine, we have clinical laboratory tools to precisely characterize HER2 status as Positive, Negative, or Low in any breast cancer. Our findings show that high resolution testing can provide an accurate HER2 genomic subtype for every tumor so no patient has to endure the uncertainty of HER2 equivocal results.” The abstract, which outlines the high resolution testing used to identify the genomic subtype of breast tumors, will be presented by Dr. Gunn as follows: Title: A clinically validated DNA microarray for high-resolution HER2 testing defines a new genomic subtype in high- risk breast cancer with equivocal results by IHC and FISH Abstract Number: P1-09-18 Date & Time: Thursday, December 7th from 5:00 p.m. to 7:00 p.m. The San Antonio Breast Cancer Symposium will take place December 6-10, 2016 in San Antonio, Texas. ABOUT ResearchDx/PacificDx ResearchDx was founded to equip biopharmaceutical companies with the knowledge and expertise to develop and manufacture the next generation of companion diagnostic products. As the preeminent Companion Diagnostics Organization, ResearchDx offers management services for every stage of the diagnostic development process—from initial assay concept and discovery through clinical research and international regulatory approval. Learn how ResearchDx personalizes medicine at http://researchdx.com/about-us/. Recognized as a leader in the design and implementation of high-complexity testing, the PacificDx Laboratory provides outsourcing services to pathology groups and biopharma allowing seamless integration of molecular assays into their existing test menus http://pacificdx.com


Awad M.M.,Dana-Farber Cancer Institute | Awad M.M.,Harvard University | Oxnard G.R.,Dana-Farber Cancer Institute | Oxnard G.R.,Harvard University | And 14 more authors.
Journal of Clinical Oncology | Year: 2016

Purpose: Non-small-cell lung cancers (NSCLCs) harboring mutations in MET exon 14 and its flanking introns may respond to c-Met inhibitors. We sought to describe the clinical, pathologic, and genomic characteristics of patients with cancer with MET exon 14 mutations. Patients and Methods: We interrogated next-generation sequencing results from 6,376 cancers to identify those harboring MET exon 14 mutations. Clinical characteristics of MET exon 14 mutated NSCLCs were compared with those of NSCLCs with activating mutations in KRAS and EGFR. Co-occurring genomic mutations and copy number alterations were identified. c-Met immunohistochemistry and real-time polymerase chain reaction to detect exon 14 skipping were performed where sufficient tissue was available. Results: MET exon 14 mutations were identified in 28 of 933 nonsquamous NSCLCs (3.0%) and were not seen in other cancer types in this study. Patients with MET exon 14-mutated NSCLC were significantly older (median age, 72.5 years) than patients with EGFR-mutant (median age, 61 years; P <.001) or KRAS-mutant NSCLC (median age, 65 years; P <.001). Among patients with MET exon 14 mutations, 68% were women, and 36% were never-smokers. Stage IV MET exon 14-mutated NSCLCs were significantly more likely to have concurrent MET genomic amplification (mean ratio of MET to chromosome 7, 4.3) and strong c-Met immunohistochemical expression (mean H score, 253) than stage IA to IIIB MET exon 14-mutated NSCLCs (mean ratio of MET to chromosome 7, 1.4; P=.007; mean H score, 155; P=.002) and stage IV MET exon 14-wild-type NSCLCs (mean ratio of MET to chromosome 7, 1.2; P <.001; mean H score, 142; P <.001). A patient whose lung cancer harbored a MET exon 14 mutation with concurrent genomic amplification of the mutated MET allele experienced a major partial response to the c-Met inhibitor crizotinib. Conclusion: MET exon 14 mutations represent a clinically unique molecular subtype of NSCLC. Prospective clinical trials with c-Met inhibitors will be necessary to validate MET exon 14 mutations as an important therapeutic target in NSCLC. © 2016 American Society of Clinical Oncology. All rights reserved.


Moore M.W.,ResearchDx | Babu D.,University of Alberta | Cotter P.D.,ResearchDx
Personalized Medicine | Year: 2012

Therapeutics harnessing the power of personalized medicine have the potential to revolutionize healthcare. Companion diagnostics are critical to this goal and are increasingly relied upon to ensure the effective, safe development and use of a personalized therapeutic. Companion diagnostics are the focus of several recent regulatory guidance documents; the drug-diagnostic codevelopment process has become increasingly relevant and necessary. Despite this, the promise of companion diagnostics has not been fully realized and there are multiple difficulties that still need resolution. The path to codevelop a successful companion diagnostic with its complementary drug is complex, fragmented and fraught with several challenges. In this article, we discuss the logistic, strategic business, regulatory and financial challenges involved in drug-companion diagnostic codevelopment. © 2012 Future Medicine Ltd.


PubMed | ResearchDx
Type: | Journal: Frontiers in oncology | Year: 2013

The phosphatase and tensin homolog gene (PTEN) on chromosome 10q23.3 is a negative regulator of the PIK3/Akt survival pathway and is the most frequently deleted tumor suppressor gene in prostate cancer. Monoallelic loss of PTEN is present in up to 60% of localized prostate cancers and complete loss of PTEN in prostate cancer is linked to metastasis and androgen-independent progression. Studies on the genomic status of PTEN in prostate cancer initially used a two-color fluorescence in situ hybridization (FISH) assay for PTEN copy number detection in formalin fixed paraffin embedded tissue preparations. More recently, a four-color FISH assay containing two additional control probes flanking the PTEN locus with a lower false-positive rate was reported. Combined with the detection of other critical genomic biomarkers for prostate cancer such as ERG, androgen receptor, and MYC, the evaluation of PTEN genomic status has proven to be invaluable for patient stratification and management. Although less frequent than allelic deletions, point mutations in the gene and epigenetic silencing are also known to contribute to loss of PTEN function, and ultimately to prostate cancer initiation. Overall, it is clear that PTEN is a powerful biomarker for prostate cancer. Used as a companion diagnostic for emerging therapeutic drugs, FISH analysis of PTEN is promisingly moving human prostate cancer closer to more effective cancer management and therapies.

Loading ResearchDx collaborators
Loading ResearchDx collaborators