News - KRAS A146V - LARVOL VERI

7ms

Prognostic value of specific KRAS mutations in patients with colorectal peritoneal metastases. (PubMed, ESMO Open)

In patients with CRC PM, different KRAS mutation subgroups can be determined according to specific codon substitution, with some mutations (KRASMUT1) that could have a similar prognosis to wild-type patients. These findings should be further investigated in larger series.

7 months ago

Journal

KRAS (KRAS proto-oncogene GTPase)

KRAS mutation • KRAS G12C • KRAS G12D • KRAS G12V • KRAS wild-type • KRAS G12R • KRAS G12A • KRAS G12 • KRAS G12S • KRAS Q61H • KRAS A146T • KRAS A146V • KRAS G13A • KRAS G13C

9ms

Computational Exploration of Single-Nucleotide Polymorphisms in the Human hRAS Gene: Implications and Insights. (PubMed, Cureus)

Therefore, the seven SNPs were identified as high-risk SNPs. Conclusions Given that SNPs have the potential to be candidates for cellular alterations brought on by mutations that are associated with cancer, this study provides vital information about how SNPs might be utilized as a diagnostic marker for cancer.

9 months ago

Journal

KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • HRAS (Harvey rat sarcoma viral oncogene homolog)

NRAS Q61K • NRAS Q61 • KRAS Q61H • NRAS G13 • NRAS Q61H • KRAS A146V • NRAS A146 • KRAS Q61K

1year

Small nucleotide, copy number and structural variants cooperate to hijack driver genes in extramedullary progression of myeloma (IMW 2023)

The MAPK DM, high TMB and persistent genomic instability suggest roles for MAPK-targeted therapies, immunotherapies and DNA damage repair pathway inhibitors, respectively, in EMD. Recurrent codon 61 mutations in RAS suggest a specific role in EMD progression.

1 year ago

Tumor mutational burden • IO biomarker

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • NRAS (Neuroblastoma RAS viral oncogene homolog) • FGFR3 (Fibroblast growth factor receptor 3) • CCND2 (Cyclin D2) • CCND3 (Cyclin D3)

TP53 mutation • BRAF V600E • KRAS mutation • TMB-H • NRAS mutation • BRAF V600 • RAS mutation • NRAS Q61 • KRAS G13 • NRAS G13 • KRAS Q61 • BRAF G469A • NRAS G13R • KRAS A146V • NRAS A146 • Chr del(1p)

over1year

Describing the molecular landscape of extramedullary multiple myeloma using whole genome sequencing: Insights into pathology and therapeutic targets (AACR 2023)

MAPK DM were frequent in EMD, and detectable in ctDNA, suggesting roles for both MAPK-targeted therapies and for ctDNA as a biomarker in these patients. A high TMB was identified in patients lacking a MAPK driver mutation; immunotherapy should be considered in this subgroup.

over 1 year ago

Tumor mutational burden • IO biomarker

TP53 mutation • BRAF V600E • KRAS mutation • TMB-H • NRAS mutation • BRAF V600 • NRAS Q61 • KRAS G13 • NRAS G13 • KRAS Q61 • BRAF G469A • NRAS G13R • KRAS A146V • NRAS A146 • Chr del(1p)

almost2years

Phase II Trial of Regorafenib and Oral Methotrexate in Previously Treated Advanced KRAS Mutant Non-Small Cell Lung Cancer (IASLC-TTLC 2023)

In addition, the study did not meet its primary endpoint. Analysis of circulating tumor DNA (ctDNA) dynamics during study treatment is ongoing.

almost 2 years ago

P2 data • Metastases

KRAS (KRAS proto-oncogene GTPase)

KRAS mutation • KRAS G12D • KRAS G12V • KRAS G12R • KRAS G12S • KRAS A146V • KRAS Q61L

Stivarga (regorafenib) • methotrexate

almost2years

Driver and targetable alterations in Chinese patients with small bowel carcinoma. (PubMed, J Cancer Res Clin Oncol)

Taken together, our work provided a comprehensive analysis of driver and targetable alterations in SBA, which can facilitate the practice of precision oncology in this challenging disease.

almost 2 years ago

Journal

HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • ZKSCAN1 (Zinc Finger With KRAB And SCAN Domains 1)

KRAS mutation • KRAS G12C • BRAF mutation • HER-2 amplification • PIK3CA mutation • KRAS wild-type • RAS mutation • RAS wild-type • KRAS G12 • KRAS A146 • KRAS Q61 • KRAS A146V • KRAS K117 • MET fusion • PIK3CA N345K • PIK3CA Q546

almost2years

Branchioma: A Series of 23 Cases Illustrating Frequent Loss of the Retinoblastoma 1 (Rb1) (USCAP 2023)

Recent developments support b ranchioma as a true neoplasm, most likely derived from the rudimental embryological structures of endoderm and mesoderm. Frequent Rb1 loss by immunohistochemistry represents a true pitfall and potential confusion with other Rb1-deficient head and neck neoplasms (i.e., spindle cell lipoma), especially in small biopsy samples.

almost 2 years ago

Clinical • BRCA Biomarker

KRAS (KRAS proto-oncogene GTPase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • PTEN (Phosphatase and tensin homolog) • AR (Androgen receptor) • HRAS (Harvey rat sarcoma viral oncogene homolog) • RB1 (RB Transcriptional Corepressor 1) • ARID1A (AT-rich interaction domain 1A) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • PTCH1 (Patched 1) • MSH6 (MutS homolog 6) • KMT2C (Lysine Methyltransferase 2C) • CD34 (CD34 molecule) • PLCG2 (Phospholipase C Gamma 2) • XRCC2 (X-Ray Repair Cross Complementing 2) • TP63 (Tumor protein 63) • FANCG (FA Complementation Group G) • BMPR1A (Bone Morphogenetic Protein Receptor Type 1A) • CHD2 (Chromodomain Helicase DNA Binding Protein 2) • PHOX2B (Paired Like Homeobox 2B)

KRAS A146V • NF2 negative

TruSight Oncology 500 Assay

2years

Prevalence and patterns of mutations in RAS/RAF/MEK/ERK/MAPK signaling pathway in colorectal cancer in North Africa. (PubMed, BMC Cancer)

KRAS mutated CRC patients in North Africa have been identified with incidence closer to the European figures. Beside established anti-CRC treatment, better understanding of the causality of CRC can be established by combining epidemiology and genetic/epigenetic on CRC etiology. This approach may be able to significantly reduce the burden of CRC in North Africa.

2 years ago

Review • Journal

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog)

KRAS mutation • KRAS G12C • BRAF mutation • NRAS mutation • KRAS G12D • KRAS G12V • RAS mutation • KRAS G12A • KRAS G12 • NRAS Q61 • KRAS G12S • KRAS exon 2 mutation • NRAS G12D • NRAS G13 • NRAS Q61L • KRAS A59T • KRAS A146T • NRAS A146T • NRAS G13R • KRAS A146V • KRAS G13C • KRAS exon 3 mutation • KRAS exon 4 mutation • NRAS A146 • NRAS A59 • KRAS Q61L • NRAS G12S • KRAS A146P

over2years

Relationship between perioperative oncological evaluation and recurrence using circulating tumor DNA with KRAS mutation in patients with colorectal cancer. (PubMed, Cancer Med)

In this study, pathological tumor size, tumor depth, and stage were correlated with preoperative MAF of KRAS, but it was unreliable to predict recurrence by detection of ctDNA with KRAS mutation in the perioperative period of colorectal surgery.

over 2 years ago

Journal • Circulating tumor DNA

KRAS (KRAS proto-oncogene GTPase)

KRAS mutation • KRAS G12C • KRAS G12D • KRAS G12V • KRAS G12A • KRAS G12 • KRAS G12S • KRAS Q61H • KRAS A146T • KRAS A146V • KRAS exon 4 mutation

over2years

Landscape of concomitant driver mutations in EGFR-mutated NSCLCs (AACR 2022)

In our large cohort study, we present the landscape of EGFR+ dual drivers and their associated clinical and genomic features and survival outcomes, which could aid in therapeutic decisions and facilitate the development of combination therapies.

over 2 years ago

Tumor Mutational Burden

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • RB1 (RB Transcriptional Corepressor 1) • TSC2 (TSC complex subunit 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • ARID2 (AT-Rich Interaction Domain 2)

KRAS mutation • EGFR mutation • KRAS G12C • BRAF mutation • HER-2 amplification • PIK3CA mutation • MET amplification • MET exon 14 mutation • ROS1 fusion • KRAS G12A • MET mutation • PIK3CA amplification • HER-2 S310F • KRAS G12 • KRAS G12S • KRAS G13 • EGFR mutation + PIK3CA mutation • HER-2 exon 20 mutation • KRAS A146T • KRAS A146V • HER-2 exon 23 mutation

3years

Genomic alteration of a metastatic gastric-type cervical adenocarcinoma: hints and personalized treatment options (ESGO 2021)

In the absence of a specific treatment guideline for GAS we initiated a cisplatin, paclitaxel and bevacizumab treatment combination. Based on the NGS results, in case of treatment failure, a MAPK targeted treatment by a MEK inhibitor could be considered.

3 years ago

PD(L)-1 Biomarker • IO biomarker

HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A)

TP53 mutation • STK11 mutation • KRAS exon 2 mutation • HER-2 exon 20 mutation • KRAS A146V

VENTANA PD-L1 (SP263) Assay

Avastin (bevacizumab) • cisplatin • paclitaxel

4years

Analysis of Molecular Pretreated Tumor Profiles as Predictive Biomarkers of Therapeutic Response and Survival Outcomes after Neoadjuvant Therapy for Rectal Cancer in Moroccan Population. (PubMed, Dis Markers)

In addition, this shows that high p53 expression in the pretreatment biopsy was associated with an incomplete response in surgical resection specimens after neoadjuvant treatment, and a HER-2 score 3+ can be a predictive factor of distant metastasis and local recurrence. Larger, prospective, and more studies are needed.

4 years ago

Clinical • Journal

HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog)

KRAS mutation • HER-2 overexpression • BRAF mutation • NRAS mutation • HER-2 expression • TP53 expression • KRAS A146T • NRAS A146T • KRAS A146V • NRAS A146

over4years

A Novel Multiplex droplet digital PCR Assay to Identify and Quantify KRAS Mutations in Clinical Specimens. (PubMed, J Mol Diagn)

We have validated 13 mutations (G12S, G12R, G12D, G12A, G12V, G12C, G13D, G60V, Q61H, Q61L, A146V, A146T, and A146P) and focal KRAS amplifications by conducting this assay in a cohort of 100 DNA samples extracted from fresh frozen tumor biopsies, formaldehyde-fixed, paraffin-embedded tissue, and liquid biopsy specimens. Despite its modest lower limit of detection (around 1%), this assay will be a rapid cost-effective means to infer the purity of biopsy specimens carrying KRAS mutations and can be utilized in non-invasive serial monitoring of circulating tumor DNA to evaluate clinical response and/or detect early signs of relapse.

over 4 years ago

Clinical • Journal

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase)

KRAS mutation • KRAS G12V • KRAS G12A • KRAS G12 • KRAS G12S • KRAS Q61H • KRAS exon 2 mutation • KRAS A146T • KRAS A146V • KRAS Q61L

over4years

[VIRTUAL] RNA AND DNA SEQUENCING REVEAL MARKERS OF RESPONSE TO THE XPO1 INHIBITOR ELTANEXOR IN PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA (RRMM) (EHA 2020)

As anticipated, similar response signatures were seen between eltanexor and selinexor. Follow-up studies to further understand the biologic significance of altered protein activities and validate the mutations putatively associated with response in larger sample sets will be conducted.

over 4 years ago

Clinical • IO biomarker

KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BCL6 (B-cell CLL/lymphoma 6) • TOP2A (DNA topoisomerase 2-alpha) • NOTCH3 (Notch Receptor 3) • USH2A (Usherin)

KRAS mutation • KRAS G12D • KRAS G12 • NRAS Q61 • NRAS G12D • NRAS Q61L • NOTCH3 mutation • KRAS A146V • KRAS Q61L

Xpovio (selinexor) • eltanexor (KPT-8602)