scholarly journals Necessity of Microdissecting Different Tumor Components in Pulmonary Tumor Pyrosequencing

2016 ◽  
Vol 2016 ◽  
pp. 1-5
Author(s):  
Dahui Qin ◽  
Zhong Zheng ◽  
Shanxiang Shen ◽  
Prudence Smith ◽  
Farah K. Khalil
Keyword(s):  
Gene Mutations ◽  
Molecular Testing ◽  
Tissue Sampling ◽  
Wild Type ◽  
Kras Mutations ◽  
Viral Oncogene ◽  
Pulmonary Tumor ◽  
New Challenges ◽  
Murine Sarcoma ◽  
Viral Oncogene Homolog

Microdissection is a useful method in tissue sampling prior to molecular testing. Tumor heterogeneity imposes new challenges for tissue sampling. Different microdissecting methods have been employed in face of such challenge. We improved our microdissection method by separately microdissecting the morphologically different tumor components. This improvement helped the pyrosequencing data analysis of two specimens. One specimen consisted of both adenocarcinoma and neuroendocrine components. When both tumor components were sequenced together for KRAS (Kirsten rat sarcoma viral oncogene homolog) gene mutations, the resulting pyrogram indicated that it was not a wild type, suggesting that it contained KRAS mutation. However, the pyrogram did not match any KRAS mutations and a conclusion could not be reached. After microdissecting and testing the adenocarcinoma and neuroendocrine components separately, it was found that the adenocarcinoma was positive for KRAS G12C mutation and the neuroendocrine component was positive for KRAS G12D mutation. The second specimen consisted of two morphologically different tumor nodules. When microdissected and sequenced separately, one nodule was positive for BRAF (v-raf murine sarcoma viral oncogene homolog B1) V600E and the other nodule was wild type at the BRAF codon 600. These examples demonstrate that it is necessary to microdissect morphologically different tumor components for pyrosequencing.

scholarly journals Ring Finger Protein 149 Is an E3 Ubiquitin Ligase Active on Wild-type v-Raf Murine Sarcoma Viral Oncogene Homolog B1 (BRAF)

2012 ◽  
Vol 287 (28) ◽  
pp. 24017-24025 ◽  
Author(s):  
Seung-Woo Hong ◽  
Dong-Hoon Jin ◽  
Jae-Sik Shin ◽  
Jai-Hee Moon ◽  
Young-Soon Na ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
E3 Ubiquitin Ligase ◽  
Ring Finger ◽  
Ring Finger Protein ◽  
Wild Type ◽  
Viral Oncogene ◽  
Finger Protein ◽  
Type V ◽  
Murine Sarcoma ◽  
Viral Oncogene Homolog

scholarly journals Multiplex Picodroplet Digital PCR to Detect KRAS Mutations in Circulating DNA from the Plasma of Colorectal Cancer Patients

2013 ◽  
Vol 59 (12) ◽  
pp. 1722-1731 ◽  
Author(s):  
Valerie Taly ◽  
Deniz Pekin ◽  
Leonor Benhaim ◽  
Steve K Kotsopoulos ◽  
Delphine Le Corre ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Digital Pcr ◽  
Blood Collection ◽  
Circulating Dna ◽  
Single Mutation ◽  
Plasma Samples ◽  
Wild Type ◽  
Kras Mutations ◽  
Viral Oncogene ◽  
Viral Oncogene Homolog

BACKGROUND Multiplex digital PCR (dPCR) enables noninvasive and sensitive detection of circulating tumor DNA with performance unachievable by current molecular-detection approaches. Furthermore, picodroplet dPCR facilitates simultaneous screening for multiple mutations from the same sample. METHODS We investigated the utility of multiplex dPCR to screen for the 7 most common mutations in codons 12 and 13 of the KRAS (Kirsten rat sarcoma viral oncogene homolog) oncogene from plasma samples of patients with metastatic colorectal cancer. Fifty plasma samples were tested from patients for whom the primary tumor biopsy tissue DNA had been characterized by quantitative PCR. RESULTS Tumor characterization revealed that 19 patient tumors had KRAS mutations. Multiplex dPCR analysis of the plasma DNA prepared from these samples identified 14 samples that matched the mutation identified in the tumor, 1 sample contained a different KRAS mutation, and 4 samples had no detectable mutation. Among the tumor samples that were wild type for KRAS, 2 KRAS mutations were identified in the corresponding plasma samples. Duplex dPCR (i.e., wild-type and single-mutation assay) was also used to analyze plasma samples from patients with KRAS-mutated tumors and 5 samples expected to contain the BRAF (v-raf murine sarcoma viral oncogene homolog B) V600E mutation. The results for the duplex analysis matched those for the multiplex analysis for KRAS-mutated samples and, owing to its higher sensitivity, enabled detection of 2 additional samples with low levels of KRAS-mutated DNA. All 5 samples with BRAF mutations were detected. CONCLUSIONS This work demonstrates the clinical utility of multiplex dPCR to screen for multiple mutations simultaneously with a sensitivity sufficient to detect mutations in circulating DNA obtained by noninvasive blood collection.

scholarly journals Treatment of NRAS-mutated advanced or metastatic melanoma: rationale, current trials and evidence to date

2017 ◽  
Vol 9 (7) ◽  
pp. 481-492 ◽  
Author(s):  
Amélie Boespflug ◽  
Julie Caramel ◽  
Stephane Dalle ◽  
Luc Thomas
Keyword(s):  
Metastatic Melanoma ◽  
Cytotoxic Chemotherapy ◽  
Disease Course ◽  
Line Treatment ◽  
First Line ◽  
Viral Oncogene ◽  
Melanoma Patients ◽  
Murine Sarcoma ◽  
Review Current ◽  
Viral Oncogene Homolog

The disease course of BRAF (v-raf murine sarcoma viral oncogene homolog B1)-mutant melanoma has been drastically improved by the arrival of targeted therapies. NRAS (neuroblastoma RAS viral oncogene homolog)-mutated melanoma represents 15–25% of all metastatic melanoma patients. It currently does not have an approved targeted therapy. Metastatic patients receive immune-based therapies as first-line treatments, then cytotoxic chemotherapy like carboplatin/paclitaxel (C/P), dacarbazine (DTIC) or temozolomide (TMZ) as a second-line treatment. We will review current preclinical and clinical developments in NRAS-mutated melanoma, and analyze ongoing clinical trials that are evaluating the benefit of different targeted and immune-based therapies, either tested as single agents or in combination, in NRAS-mutant melanoma.

scholarly journals BRAF and KRAS mutations in metastatic colorectal cancer: future perspectives for personalized therapy

2020 ◽  
Vol 8 (3) ◽  
pp. 192-205 ◽  
Author(s):  
Zi-Nan Li ◽  
Lin Zhao ◽  
Li-Feng Yu ◽  
Min-Jie Wei
Keyword(s):  
Colorectal Cancer ◽  
Clinical Trials ◽  
Survival Rate ◽  
Metastatic Colorectal Cancer ◽  
Early Stage ◽  
Unmet Need ◽  
Growth Factor Receptor ◽  
Kras Mutations ◽  
Viral Oncogene ◽  
Viral Oncogene Homolog

Abstract Colorectal cancer (CRC) is one of the most commonly diagnosed cancers worldwide and 30% of patients with CRC experience metastasis. Patients with metastatic colorectal cancer (mCRC) have a 5-year overall survival rate of <10%. V-raf murine sarcoma viral oncogene homolog B1 (BRAF) and V-Ki-ras2 Kirsten ratsarcoma viral oncogene homolog (KRAS) mutations are mostly studied in mCRC, as clinical trials found that first-line chemotherapy with anti-epidermal growth factor receptor agent confers limited efficacy for mCRC. Treatment decisions for early-stage mCRC do not consider BRAF or KRAS mutations, given the dramatically poor prognosis conferred by these mutations in clinical trials. Thus, it is necessary to identify patients with mCRC harboring BRAF or KRAS mutations to formulate rational therapeutic strategies to improve prognosis and survival. BRAF and KRAS mutations occur in ∼10% and ∼44% of patients with mCRC, respectively. Although the survival rate of patients with mCRC has improved in recent years, the response and prognosis of patients with the aforementioned mutations are still poor. There is a substantial unmet need for prospective personalized therapies for patients with BRAF- or KRAS-mutant mCRC. In this review, we focus on BRAF and KRAS mutations to understand the mechanisms underlying resistance and improving the response rate, outcomes, and prognosis of patients with mCRC bearing these mutations and to discuss prospective personalized therapies for BRAF- and KRAS-mutant mCRC.

scholarly journals V-raf murine sarcoma viral oncogene homolog B (BRAF) mutations in hairy cell leukaemia

2015 ◽  
Vol 58 (1) ◽  
pp. 62
Author(s):  
Neeraj Arora ◽  
Sheila Nair ◽  
Rekha Pai ◽  
Sukesh Nair ◽  
Auro Viswabandya ◽  
...  
Keyword(s):  
Hairy Cell Leukaemia ◽  
Cell Leukaemia ◽  
Hairy Cell ◽  
Braf Mutations ◽  
Viral Oncogene ◽  
Murine Sarcoma ◽  
Viral Oncogene Homolog

scholarly journals Atypical BRAF and NRAS Mutations in Mucosal Melanoma

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1133 ◽  
Author(s):  
Nicolas Dumaz ◽  
Fanélie Jouenne ◽  
Julie Delyon ◽  
Samia Mourah ◽  
Armand Bensussan ◽  
...  
Keyword(s):  
Mapk Pathway ◽  
Mucosal Melanoma ◽  
Mitogen Activated Protein Kinase ◽  
Nras Mutation ◽  
Viral Oncogene ◽  
Mitogen Activated Protein ◽  
Murine Sarcoma ◽  
Worse Prognosis ◽  
Viral Oncogene Homolog

Primary mucosal melanomas represent a minority of melanomas, but have a significantly worse prognosis than cutaneous melanomas. A better characterization of the molecular pathogenesis of this melanoma subtype could help us understand the risk factors associated with the development of mucosal melanomas and highlight therapeutic targets. Because the Mitogen-Activated Protein Kinase (MAPK) pathway plays such a significant role in melanoma development, we explore v-raf murine sarcoma viral oncogene homolog B (BRAF) and neuroblastoma RAS viral oncogene homolog (NRAS) mutations in mucosal melanoma and compare them to the mutation profiles in cutaneous melanoma and other tumors with BRAF and NRAS mutations. We show that in addition to being less frequent, BRAF and NRAS mutations are different in mucosal melanoma compared to cutaneous melanomas. Strikingly, the BRAF and NRAS mutation profiles in mucosal melanoma are closer to those found in cancers such as lung cancer, suggesting that mutations in mucosal melanoma could be linked to some genotoxic agents that remain to be identified. We also show that the atypical BRAF and NRAS mutations found in mucosal melanomas have particular effects on protein activities, which could be essential for the transformation of mucosal melanocytes.

Primary Mucinous Cystadenocarcinoma of the Breast: A Rare Case Report With Review of Literature

2021 ◽  
pp. 106689692199165
Author(s):  
Ekta Jain ◽  
Abhishek Kumar ◽  
Raajul Jain ◽  
Shivani Sharma
Keyword(s):  
Mucinous Cystadenocarcinoma ◽  
Whole Body ◽  
Molecular Testing ◽  
Whole Body Imaging ◽  
Cytokeratin 20 ◽  
Braf Mutations ◽  
Palpable Mass ◽  
Viral Oncogene ◽  
First Case ◽  
Viral Oncogene Homolog

Primary mucinous cystadenocarcinoma (MCA) of the breast is a rare variant of breast carcinoma known to have a favorable prognosis despite showing a basal-like phenotype. We describe a case of MCA breast in a 45-year-old female with a palpable mass in the breast. On the basis of the histopathological and immunohistochemical evaluation of a lumpectomy specimen with the absence of mass anywhere else on whole-body imaging, a diagnosis of primary MCA was rendered. Mismatch repair protein evaluation showed this tumor to be microsatellite stable. Molecular testing revealed the absence of Kirsten rat sarcoma viral oncogene homolog (KRAS), neuroblastoma RAS viral oncogene homolog (NRAS), and v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutations. To date only 27 cases of MCA breast have been reported. To the best of our knowledge, ours is the first case documenting diffuse Cytokeratin 20 (CK20) positivity, microsatellite stability, and the absence of KRAS, NRAS, and BRAF mutations in these tumors. The rarity of this tumor further evokes an interest in this case. A better understanding of the disease warrants a review of more cases with longer follow-ups.

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