scholarly journals Concomitant Rare KRAS and BRAF Mutations in Lung Adenocarcinoma: A Case Report

2020 ◽  
Vol 1 (1) ◽  
pp. 36-42
Author(s):  
Antonino Iaccarino ◽  
Pasquale Pisapia ◽  
Marco De Felice ◽  
Francesco Pepe ◽  
Gianluca Gragnano ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Ct Scanning ◽  
Limited Data ◽  
Braf Mutations ◽  
Right Lobe ◽  
Exon 4 ◽  
Total Body ◽  
Exon 11 ◽  
Oncology Unit ◽  
Kras Exon

In July 2020, an active smoker, 63-year old man was admitted to the oncology unit of A.O.R.N. Sant’Anna e San Sebastiano (Caserta, Italy). Chest radiology highlighted right pleural effusion. Total-body CT scanning revealed a solid lesion with lobulated contours in the apical segment of the upper right lobe. The patient’s oncologist requested a molecular assessment of EGFR, ALK, ROS1, BRAF, and KRAS, as well as an evaluation of PD-L1 expression level. To this end, we carried out NGS analysis, on DNA extracted from cytospins, by adopting a custom-designed NGS panel (SiRe®). Overall, no actionable mutations in the tested genes were identified. Conversely, concomitant BRAF exon 11 p.G469A and a KRAS exon 4 p.A146T mutations were detected. Owing to the limited data on the presence of KRAS exon 4 p.A146T point mutation in lung adenocarcinoma patients, a further molecular confirmatory analysis was carried out with a dedicated KRAS cartridge on a fully automated real time polymerase chain reaction. When DNA was extracted from the TTF-1 positive tumor cell slide, the same KRAS alteration was observed. Unfortunately, the patient died in August 2020 before having the chance to start any type of treatment.

Analysis of KRAS/NRAS and BRAF mutations in the phase III PRIME study of panitumumab (pmab) plus FOLFOX versus FOLFOX as first-line treatment (tx) for metastatic colorectal cancer (mCRC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3511-3511 ◽  
Author(s):  
Kelly S. Oliner ◽  
Jean-Yves Douillard ◽  
Salvatore Siena ◽  
Josep Tabernero ◽  
Ronald L. Burkes ◽  
...  
Keyword(s):  
Braf Mutation ◽  
Predictive Biomarker ◽  
Primary Objective ◽  
Phase Iii ◽  
Braf Mutations ◽  
Exon 2 ◽  
Mutation Status ◽  
Exon 4 ◽  
Kras Exon ◽  
Clinical Trial Information

3511 Background: Analysis of a phase III pmab monotherapy study indicated that KRAS and NRAS mutations beyond KRAS exon 2 may be predictive of pmab efficacy (Peeters et al, 2013). Methods: The primary objective of this prospectively defined retrospective analysis of PRIME was to assess the effect of pmab + FOLFOX vs FOLFOX on overall survival (OS) in pts with mCRC based on RAS (KRAS or NRAS) or BRAF mutation status. "Gold standard" bidirectional Sanger sequencing and WAVE-based SURVEYOR Scan Kits from Transgenomic (conducted independently) were used to detect mutations in KRAS exon 3, exon 4; NRAS exon 2, exon 3, exon 4; and BRAF exon 15. Results: RAS ascertainment rate was 90%. Tx HRs for pts with WT RAS were 0.78 (95% CI, 0.62 - 0.99; p = 0.04) for OS (median gain of 5.8 months in the pmab arm) and 0.72 (95% CI, 0.58 - 0.90; p = < 0.01) for PFS. Tx HRs for WT KRAS exon 2/mutant (MT) other RAS were 1.29 (95% CI, 0.79 - 2.10; p = 0.31) for OS and 1.28 (95% CI, 0.79 - 2.07; p = 0.32) for PFS. Tx HRs for pts with WT or MT BRAF were inconsistent with a predictive biomarker (Table). Prognostic effects of the tested biomarkers will be presented. Conclusions: A statistically significant OS benefit was observed in pts with WT RAS mCRC treated with pmab + FOLFOX vs FOLFOX. Pmab is unlikely to benefit pts with any RAS mutations. In this analysis, BRAF mutation had no predictive value. Clinical trial information: NCT00364013. [Table: see text]

The prevalence RAS and BRAF mutations among patients in the Middle East and Northern Africa with metastatic colorectal cancer.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 598-598
Author(s):  
Tamer Garawin ◽  
Kimberly Lowe ◽  
George Kafatos ◽  
Samuel Murray
Keyword(s):  
Colorectal Cancer ◽  
Saudi Arabia ◽  
Middle East ◽  
Wild Type ◽  
Braf Mutations ◽  
Real World Data ◽  
Exon 2 ◽  
Ras Mutation ◽  
Exon 4 ◽  
Kras Exon

598 Background: Anti-EGFR therapies are recommended for metastatic colorectal cancer (mCRC) patients with confirmed wild-type RAS (exons 2, 3, 4 of KRAS and NRAS) status. There is limited published information on the prevalence of RAS mutations using real world data. The objective of this study was estimate the prevalence of RAS and BRAF mutations among patients with mCRC in the Middle East and Northern Africa (MENA) in an effort to inform the rationale for biomarker testing and treatment choice. Methods: The study included 1,669 patients from August 2013 to July 2015 with mCRC from Algeria, Bahrain, Egypt, Jordan, Kuwait, Lebanon, Libya, Morocco, Oman, Qatar, Saudi Arabia, and the United Arab Emeritus. Information on RAS mutation status was obtained from one pathology lab using High Resolution Melting Analysis. Extended RAS analysis was conducted in a subset of patients, including: overall RAS (exon 2, 3, 4 of KRAS and NRAS; n = 750), KRAS exon 2 (n = 750), KRAS exon 3 and 4 (n = 507), NRAS exon 2, 3, and 4 (n = 507), and BRAF exon 15 (n = 78). The proportion of patients with each mutation was summarized. Results: The overall RAS mutation in the full sample was 35.3% (n = 589/1669). The observed mutation for KRAS exon 2 in a subset of patients with extended RAS analysis (n = 750) was 32.4% (243/750). Out of the subjects with wild-type exon 2 (n = 507), the observed mutations rates were as follows: KRAS exon 4 (20/507 = 3.9%), KRAS exon 3 (13/507 = 2.6%), NRAS exon 2 (7/507 = 1.4%), NRAS exon 3 (6/507 = 1.2%), and NRAS exon 4 (0%). The prevalence of BRAF exon 15 was 3.8% (3/78). The most robust data on specific RAS mutations was obtained from Algeria, Egypt, and Saudi Arabia. The prevalence of KRAS exon 2 mutations in these countries was as follows: Algeria (n = 33/86 = 38.4%), Egypt (n = 83/303 = 27.4%), Saudi Arabia (n = 85/245 = 34.7%). Conclusions: To our knowledge, this is the first study to evaluate the prevalence of RAS and BRAF mutations in the Middle East using real world data. The results of this descriptive study illustrate that there is variation in the prevalence of RAS and BRAF mutations in MENA.

BRAF-MAD1L1 and BRAF-ZC3H7A: novel gene fusion in Rhabdomyosarcoma and Lung adenocarcinoma

2021 ◽  
Author(s):  
Jiang Da ◽  
Hui Jin ◽  
Xinliang Zhou ◽  
Shaoshuang Fan ◽  
Mian Xu ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Gene Fusion ◽  
Tumor Resection ◽  
Kinase Domain ◽  
Rapid Progression ◽  
First Line ◽  
Case Presentation ◽  
First Case ◽  
Exon 11 ◽  
Domain Exon

Abstract Background: Rhabdomyosarcoma (RMS) and lung adenocarcinoma (LADC) epitomizes the success of cancer prevention by the development of conventional therapy, but huge challenges remain in the therapy of advanced diseases.Case presentation: We reported two cases of novel BRAF gene fusion. The first case was a 34-year-old female with RMS harboring a BRAF-MAD1L1 fusion. She suffered tumor resection, recurrence and rapid progression. The second case was a 72-year-old female with LADC harboring a BRAF-ZC3H7A fusion, and she gained rapid progression after receiving a first-line course of chemotherapy.Conclusions: These two BRAF fusions retain the intact BRAF kinase domain (exon 11-18) and showed poor prognosis in RMS and LADC.

scholarly journals Analysis of Predictive Biomarkers in Patients With Lung Adenocarcinoma From Southern Brazil Reveals a Distinct Profile From Other Regions of the Country

2019 ◽  
pp. 1-9 ◽  
Author(s):  
Tiago F. Andreis ◽  
Bruno S. Correa ◽  
Fernanda S. Vianna ◽  
Fernanda De-Paris ◽  
Marina Siebert ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Predictive Biomarkers ◽  
Egfr Mutations ◽  
Southern Brazil ◽  
Braf Mutations ◽  
Kras Mutations ◽  
Histologic Subtype ◽  
Molecular Alterations ◽  
Common Histologic Subtype ◽  
L1 Protein

PURPOSE Adenocarcinoma is the most common histologic subtype of non–small-cell lung cancer, representing 40% of all diagnoses. Several biomarkers are currently used to determine patient eligibility for targeted treatments, including analysis of molecular alterations in EGFR and ALK, as well as programmed death-ligand 1 (PD-L1) protein expression. Epidemiologic data reporting the frequency of these biomarkers in Brazilian patients with lung adenocarcinoma (LUAD) are limited, and existing studies predominantly included patients from the southeast region of the country. MATERIALS AND METHODS The goal of this study was to investigate the frequency of somatic mutations in the EGFR, KRAS, NRAS, and BRAF genes, ALK, and PD-L1 expression in a series of Brazilian patients diagnosed with LUAD predominantly recruited from centers in southern Brazil. Molecular analysis of the EGFR, KRAS, NRAS, and BRAF genes was performed by next-generation sequencing using DNA extracted from tumor tissue. Immunohistochemistry was used to detect ALK and PD-L1 expression. RESULTS Analysis of 619 tumors identified KRAS mutations in 189 (30.2%), EGFR mutations in 120 (19.16%), and BRAF mutations in 19 (3%). Immunohistochemistry demonstrated ALK and PD-L1 expression in 4% and 35.1% of patients, respectively. CONCLUSION To our knowledge, this is the first study investigating the molecular epidemiology of patients with LUAD from southern Brazil and the largest assessing the frequency of multiple predictive biomarkers for this tumor in the country. The study also reveals a distinct mutation profile compared with data originating from other regions of Brazil.

Expanded KRAS and NRAS assays increase detection of mutations that predict for resistance to therapy in colorectal cancer patients.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 519-519
Author(s):  
Garrett Larson ◽  
Anna Israyelyan ◽  
Heinz-Josef Lenz ◽  
Stephanie H. Astrow
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Targeted Therapies ◽  
Kinase Inhibitor ◽  
Meta Analysis ◽  
Screening Strategy ◽  
Nras Mutation ◽  
Braf Mutations ◽  
Exon 2 ◽  
Exon 4

519 Background: The selection of targeted therapies is guided by the analysis of somatic mutations. The identification of RAS activating mutations can be used to examine tyrosine kinase inhibitor therapeutic eligibility and prognosis. Beyond known mutations in RAS exon 2 (codons 12 and 13), the identification of additional mutations in RAS exons 3 and 4 (codons 61, 117 and 146) also predict for resistance to EGFR therapy in colorectal cancer (CRC). Meta-analysis supports screening for these additional mutations in any screening strategy prior to administration of EGFR mAb therapy in metastatic CRC patients (Sorich, MJ, et al., Ann Oncol, Aug 12, 2014). Methods: We expanded our existing allele-specific KRAS and sequencing-based NRAS assays to include codons 61, 117, and 146 and analytically validated these assays to CAP/CLIA standards. DNA, from microdissected colon tumor tissue that was wild-type for RAS exon 2, was tested for exon 3 and 4 mutations and included over 15 additional mutations. Results: Forty-two (9.1%) samples were identified as bearing either an exon 3 or 4 KRAS mutation amongst 461 colon cancer specimens. Exon 4 codon 146 mutations were more prevalent than three of the commonly screened exon 2 mutations: G12A, G12R, and G12S. Five (1.8%) of samples were identified as carrying exon 3 or 4 NRAS mutations amongst 272 colon cancer specimens. This included a single codon 146 mutation in exon 4. As is seen with exon 2, RAS mutations at exons 3 and 4 were mutually exclusive of activating BRAF mutations with ~10% of patients harboring V600E. The collection of additional data studying KRAS and NRAS mutation status is currently ongoing. Conclusions: The KRAS expanded coverage contributed an additional 5.5% to overall burden of specimens bearing mutations. The NRAS expanded coverage contributed an additional 1.8% to the mutational burden. These analyses in clinical cohorts support the observations made in a trial population (Douillard JV, et al. NEJM 369:1023-34, 2013). The expanded RAS coverage identifies additional patients unlikely to respond to EGFR-targeted therapies that would otherwise have been assessed as “no mutation detected” in using assays restricted to RAS exon 2.

Implementation of molecular testing for EGFR mutations and ALK rearrangement in lung adenocarcinoma in Brazil.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e18002-e18002
Author(s):  
Sofia Palacio ◽  
Gilberto Lopes ◽  
Edna Prado
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Practice Patterns ◽  
Egfr Mutations ◽  
Molecular Testing ◽  
Limited Data ◽  
Alk Rearrangement ◽  
First Semester ◽  
Changing Practice ◽  
Current Guidelines

e18002 Background: Lung cancer is the leading cause of cancer death worldwide. In Brazil, cancer is the second most common cause of death and there were an estimated 27,330 new cases of lung cancer in 2014. Targeted therapies have changed disease prognosis and current clinical guidelines advocate for EGFR/ALK molecular testing for all patients with advanced-stage lung adenocarcinoma. Access to this testing is often limited in the developing world. In the case of Brazil, there is limited data regarding the frequency of testing and the changes in patterns of testing overtime. Methods: De-identified data was obtained from a commercial database that surveys approximately 2,000 cancer physicians in Brazil regarding practice patterns. On average 300 physicians responded to the survey, which is conducted every 6 months, and provided information on about 18,000 patients. Subsequently, we identified patients with lung cancer and calculated the frequency of testing for EGFR mutations and ALK rearrangement from 2011 to 2016. Results: 11,684 patients with lung adenocarcinoma were analyzed from 2011 to 2016. The frequency of testing for EGFR mutations increased significantly: 12.8% (287/2,228) in 2011, 34.4% (738/2,142) in 2012, 39.2% in 2013 (822/2,092), 43.9% in 2014 (866/1,972), 53.3% (1165/2,184) in 2015, and 58% (626/1,066) for the first semester of 2016. Testing for ALK rearrangement also increased noticeably over the same period: 0% in 2011 (0/2,228) and 2012 (0/2,142), 0.9% (19/2,092) in 2013, 2.99% (59/1,972) in 2014, 5.5% (121/2,184) in 2015, and 4.8% (52/1,066) for the first semester of 2016. Conclusions: To our knowledge this is the largest data analysis regarding changing practice patterns of molecular testing for lung adenocarcinoma over time in Brazil and Latin America. The frequency of testing for EGFR mutations and ALK rearrangement has increased over the last 5 years but is still below the current guidelines recommending that all patients with advanced disease be tested. Further understanding of the barriers to testing, will hopefully lead to national strategies for universal implementation of molecular testing.

scholarly journals Third nerve paralysis due to cranial metastasis of prostate tumor

2016 ◽  
Vol 12 (1) ◽  
Author(s):  
Rao Muhammad Rashad Qamar ◽  
Qasim Mansoor ◽  
Majeed T
Keyword(s):  
Previous History ◽  
Anterior Segment ◽  
Petrous Apex ◽  
Nerve Paralysis ◽  
History Of ◽  
Total Body ◽  
The Right ◽  
Cranial Metastasis ◽  
Oncology Unit ◽  
Third Nerve

A 90 years old man presented with outward deviated right eye with droopy lid. These symptoms were developed over a period of two weeks and there was no pain behind the eye. There was no previous history of Diabetes mellitus, hypertension etc. He had a treatment for adenocarcinoma of prostate six years ago. On examination his best-corrected visual acuity was 6/60 in each eye. There was right complete third nerve paralysis with pupil involvement. Anterior segment examination showed nucleosclerotic changes on both sides. Posterior segment examination showed ARMD (dry type) in both eyes. Intraocular pressure and discs were normal. Contrast enhanced MR scan brain revealed a destructive mass at the base of skull at petrous apex on the right side extending forward to orbital apex on the same side. Total body bone scan also showed multiple metastatic lesions. Patient was referred to oncology unit for further management

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