Cancer is the result of genetic changes to deoxyribonucleic acid (DNA) that can be inherited or acquired during the lifetime. While each cancer may have unique genetic changes that could vary among cells of the same tumor type, there are certain mutations that commonly cause cancer, including mutations to tumor suppressor genes, DNA repair genes, or proto-oncogenes. Moreover, metastatic cancer cells and cells of the original cancer usually have some molecular features in common, such as the presence of changes to specific chromosomes containing DNA.
The aim of this case report was to present a molecular analysis of a renal medullary carcinoma (RMC) to direct maintenance therapy. This study used surgical specimen from an age 27 year-old African-American male with staged pT3a pN1 Mx RMC. The analysis method included NGS and molecular profiling (Caris Life Sciences). This study found that the tumor biomarker profile indicated potential benefit of gemcitabine, nabpaclitaxel, and doxorubicin, while the molecular analysis demonstrated potential targets, including PTEN loss, for MTOR inhibition. Results from the maintenance therapy led to months of CR and extension of life 14 months past diagnosis. The investigators concluded that while NGS is not feasible or necessary for every patient with a malignant tumor, additional knowledge about driver mutations may help in guiding therapy to improve survival in patients with RMC.
evolve mutations 2 crack mac
The aim of this study was to identify mutations that could inform future treatment options for patients with glioblastoma (GBM). The investigators reported that the 5-year relative survival from disease is less than 5%. This study screened DNA from 44 GBM specimens for somatic mutations in 50 oncogenes. Study demographics included specimens of the Australian Genomics and Clinical Outcome of Glioma Biospecimen Resource with primary GBM, and IDH1 wild type at position 132. The median age at diagnosis was 63.3 years (range 24 to 85 years) with males:females 30:14 and the majority of patients had total tumor resection at first surgery. The analysis method included somatic mutation profiling using the AmpliSeq Cancer Hotspot Panel v2. This study found that 9 cases had no significant mutations, while the remaining identified mutations per tumor averaged 1.5 (range 0 to 4) for 35 of 44 patients. The most frequent GAs were in TP53, PTEN, EGFR, and PIK3CA. The investigators concluded that while identifying mutations to inform treatment is feasible, future large-scale trials will be required to validate and determine the true clinical utility of this approach for implementation into clinical practice.
The aim of the study was to determine whether or not the use of a Genomic Tumor Board (GTB) was helpful in the exchange of knowledge regarding genomic testing results of advanced cancers, as well as to investigate the utility of genomic testing in clinical practice. The source of the data were medical records of patients who were managed at Mayo Clinic Center for Individualized Medicine. Patients ranged in age from 18 months to 86 years with a median of 53 years. Cases were divided between solid tumors (58%) and hematological malignancies (42%). The most common solid tumors were gynecologic and gastrointestinal in nature, while acute leukemia and lymphoma were the most common hematological malignancies. Clinical genetic testing of tumors, including next-generation sequencing panels, array comparative genomic hybridization (CGH) and whole exome sequencing (WES), was conducted in CLIA certified laboratories. These laboratories included: Foundation Medicine, Baylor College of Medicine, Caris Life Sciences, Genoptix, and Mayo Clinic. The authors found actionable mutations in 92/141 patients (65%) for whom testing was ordered. Of this number 28% (39/141) of tumors tested possess at least 1 actionable mutation. Another 8% (11/141) had informative mutations only. A quarter of patients tested (25%) had no actionable or informative targets identified by the GTB. The authors concluded that treatment decisions driven by tumor genomic analysis can lead to significant clinical benefit in patients.
The purpose of this study was to determine the genomic testing patterns for patients with advanced NSCLC diagnosed in a large multisite community-based US oncology practice and to examine the potential barriers to adherence with published biomarker guidelines. The source of the data was medical record review of patients treated within the Regional Cancer Care Associates network that consists of 15 community oncology sites throughout New Jersey and Maryland from January 1, 2013 and December 31, 2015. Participants included 814 patients with Stage IIIB and IV nonsquamous NSCLC. The median age of the patient population was 67 years, with 57% > 65 years old and 28% > 75 years old; 53% of the patients were women and 72% were white. Extensive and comprehensive NGS was used. Cell-free DNA analysis was also performed. The study revealed that of the 814 patients (89% with stage IV; 11% with stage IIIB) identified in the study, 479 (59%) met the guideline recommendations for EGFR and ALK biomarker testing; 63 (8%) underwent comprehensive genomic profiling for all four major types of alterations (point mutations, indels, fusions, and copy number amplifications). Gender, age, race, site of care, and practice size did not influence comprehensive genomic profiling frequency. The authors noted that among those not tested for EGFR and ALK, 52% received chemotherapy without documented reasons for no testing, 32% did not receive antineoplastic therapy, and 13% had insufficient tissue for genotyping. The authors concluded that genomic testing presents multiple logistical challenges, but opportunities exist for improvement in guideline adherence, possibly through new technologies such as "liquid biopsies," which the authors believed obviates the need for tissue biopsy samples in select settings.
The purpose of this study was to report the experience of the molecular tumor board (MTB), and its importance in implementation in personalized medicine. The study was conducted at the University of Alabama in Birmingham. The researchers wanted to determine if the use of a molecular tumor board was helpful before extensive molecular testing was performed. In the study, patients were reviewed by the MTB for appropriateness of comprehensive next generation sequencing (NGS) cancer gene set testing based on set criteria that was in place. The source of the data were medical records of patients treated at the institution. The vast majority of molecular testing was performed at Genomics and Pathology Services at Washington University for Comprehensive Cancer, though testing at other commercial vendors was also performed (Foundation One and Caris Life Sciences). A total of 191 cases were submitted to the MTB (50 male, 141 female; median age 57 years) and 132 cases were approved and tested. Of those tested, 46 cases (34.8%) had driver mutations that were associated with an active targeted therapeutic agent, including BRAF, PIK3CA, IDH1, KRAS, and BRCA1. 15 cases were considered for targeted therapy, 13 of which received targeted therapy. One patient experienced a near complete response. Seven of 13 had stable disease or a partial response. The authors concluded that the MTB reviews led to detection of actionable mutations and that their findings of actionable mutations may be higher because of their approach.
The aim of the study was to assess whether adjuvant treatment would improve outcomes in patients with melanoma with BRAF V600 mutations. The study used data from a double-blind, placebo-controlled, phase 3 trial that randomly assigned patients with completely resected, stage III melanoma with BRAF V600E or V600K mutations to receive oral dabrafenib plus trametinib or two matched placebo tablets. Patients were enrolled at 169 sites in 26 countries. The analysis methods included BRAF V600 mutation status confirmed by a central reference laboratory at each study site. The study demographics included 870 under randomization, with 438 patients assigned to receive combination therapy and 432 patients to receive matched placebo tablets for 12 months, with median age for each group 50 years (range 18-89 years) and 51 years (range 20-85 years), respectively. Women comprised 55% of either group. The results showed investigator-assessed 3-year relapse-free survival was significantly longer in the combination therapy group than in the placebo group, representing a 53% lower risk of relapse (HR, relapse or death, 0.47; 95% CI 0.39 to 0.58; p-value
The aim of the study was to delineate the clinicopathologic features and prognosis of BRAF mutant lung cancers compared with other genomic subsets identified through the Lung Cancer Mutation Consortium, a 14-institution collaborative effort established in 2009 to assess lung adenocarcinomas for driver genomic alterations in 10 genes (EGFR, KRAS, HER2, AKT1, BRAF, MEK1, NRAS, PIK3CA, ALK translocations, and MET amplification) to study and treat patients by their molecular subtype. The study involved 1007 patients with adenocarcinomas including patients with stage IV or recurrent adenocarcinomas of the lung and SWOG performance status 0, 1, or 2. The article made no reference to type of platform used for sequencing. Results showed 951 patient tumors were tested for BRAF mutations, in whom 21 (2.2%: 95% CI 1.4 to 3.4%) BRAF mutations were identified (17 BRAFV600E and 4 non-BRAFV600E mutations). There were 733 cases that tested positive for all 10 genes and patients whose tumors harbored BRAF mutations were older than patients with ALK rearrangements (median ages 65 and 54 years old; p-value=0.002). Significant differences were seen in gender between patients with BRAF mutations and patients with sensitizing EGFR mutations (50% patients with BRAF mutations were female, compared with 76% patients with sensitizing EGFR mutations, mid-P=0.02). BRAF mutations were more likely to occur in current or former smokers and patients with BRAF mutant tumors had the longest median OS (56 months), whereas patients with doubletons had the shortest estimated median OS (24 months). The authors concluded comprehensive genomic profiling is important in assessing patients with advanced lung adenocarcinomas. 2ff7e9595c
Comments