News - KRAS deletion - LARVOL VERI

Lfng-expressing centroacinar cell is a unique cell-of-origin for p53 deficient pancreatic cancer. (PubMed, Oncogene)

Finally, high LFNG expression is associated with high grade and poor survival in human patients. Taken together, Lfng marks a centroacinar subpopulation that is uniquely susceptible to oncogenic transformation when p53 is lost, and Lfng functions as an oncogene in all three lineages of the exocrine pancreas.

1 month ago

Journal

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • NOTCH3 (Notch Receptor 3)

TP53 mutation • KRAS mutation • TP53 deletion • KRAS deletion • KRAS mutation + TP53 mutation

The Agena iPlex HS Lung Panel on the MassARRAY System Is Able to Robustly Characterize the Molecular Profile of FFPE-Derived Lung Tumor Samples Previously Deemed QNS on Multiple NGS Platforms (AMP 2024)

The Agena iPlex HS Lung Panel on the MassARRAY System is highly tolerant of poor quantity and quality DNA, recovering and delivering accurate results on samples that would otherwise fail NGS-based analysis.

1 month ago

Next-generation sequencing

EGFR (Epidermal growth factor receptor) • 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)

KRAS mutation • EGFR mutation • BRAF mutation • PIK3CA mutation • BRAF V600 • EGFR L858R • EGFR exon 19 deletion • KRAS G12V • KRAS G12 • KRAS G13 • KRAS Q61 • KRAS deletion

TruSight Oncology 500 Assay

2ms

Prevalence and co-mutation status of MTAP deletions (COSA 2024)

MTAP deletions are common in the MoST/CaSP population, most frequently in CNS, pancreas, lung and melanoma patients. Detection of MTAP deletion was higher with the FM1&A paltform. MTAP deletions co-existed with CDKN2A deletions in >80% of the cohort.

2 months ago

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MTAP (Methylthioadenosine Phosphorylase) • MAT2A (Methionine Adenosyltransferase 2A)

CDKN2A deletion • MTAP deletion • KRAS deletion

TruSight Oncology 500 Assay

2ms

Suppression of dystroglycan function accompanies pancreatic acinar-to-ductal metaplasia and favours dysplasia development. (PubMed, J Pathol)

We conclude that dystroglycan is an important mediator of the tumour-suppressing functions of the BM during precancer evolution and that reduced dystroglycan function increases cancer risk, highlighting the dynamics of cell-BM interactions as important determinants of early cancer progression.

2 months ago

Journal

KRAS (KRAS proto-oncogene GTPase)

KRAS deletion

2ms

KRAS Loss of Heterozygosity Promotes MAPK-Dependent Pancreatic Ductal Adenocarcinoma Initiation and Induces Therapeutic Sensitivity to MEK Inhibition. (PubMed, Cancer Res)

Importantly, loss of wild-type Kras sensitized Kras mutant tumors to MEK1/2 inhibition though tumors eventually became resistant and then rapidly progressed. This study demonstrates the repressive role of wild-type KRAS during pancreatic tumorigenesis and highlights the critical impact of the presence of wild-type KRAS in both tumor progression and therapeutic response in pancreatic cancer.

2 months ago

Journal

KRAS (KRAS proto-oncogene GTPase)

KRAS mutation • KRAS wild-type • RAS wild-type • KRAS deletion

2ms

Inhibition of Ribosome Biogenesis in vivo Causes p53-Dependent Death and p53-Independent Dysfunction. (PubMed, bioRxiv)

Deletion of Nat10 in acinar cells blocked Kras -oncogene-driven pancreatic intraepithelial neoplasia and subsequent pancreatic ductal adenocarcinoma, regardless of Trp53 mutation status. Together, our results provide initial insights into how cells respond to defects in RiBi and translation in vivo .

2 months ago

Preclinical • Journal

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • RPL5 (Ribosomal Protein L5) • RPL11 (Ribosomal Protein L11)

TP53 mutation • KRAS deletion

3ms

Tumor immunogenicity regulates host immune responses, and conventional dendritic cell type 2 uptakes the majority of tumor antigens in an orthotopic lung cancer model. (PubMed, Cancer Immunol Immunother)

The majority of ZsGreen conjugated with minOVA was observed in the conventional type 2 DCs (cDC2), whereas cDC1 has minimal. These data indicate that tumor immunogenicity regulates host immune responses, and tumor neoantigen is mostly recognized by cDC2 cells, which may play a critical role in initiating antitumor immune responses in an orthotopic murine lung cancer model.

3 months ago

Preclinical • Journal

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • CD8 (cluster of differentiation 8) • CDK1 (Cyclin-dependent kinase 1) • ITGAX (Integrin Subunit Alpha X)

TP53 mutation • KRAS mutation • TP53 deletion • KRAS deletion

3ms

UBASH3B-mediated MRPL12 Y60 dephosphorylation inhibits LUAD development by driving mitochondrial metabolism reprogramming. (PubMed, J Exp Clin Cancer Res)

This study establishes MRPL12 as a novel oncogene in LUAD, contributing to LUAD pathogenesis by orchestrating mitochondrial metabolism reprogramming towards oxidative phosphorylation (OXPHOS). Furthermore, it confirms Y60 as a specific phosphorylation modification site regulating MRPL12's oncogenic functions, offering insights for the development of LUAD-specific targeted drugs and clinical interventions.

3 months ago

Journal

KRAS (KRAS proto-oncogene GTPase)

KRAS G12D • KRAS G12 • MSH3 mutation • KRAS deletion

3ms

Presence of RB1 or Absence of LRP1B Mutation Predicts Poor Overall Survival in Patients with Gastric Neuroendocrine Carcinoma and Mixed Adenoneuroendocrine Carcinoma. (PubMed, Cancer Res Treat)

The presence of LRP1B mutation was significantly associated with longer overall survival (OS), whereas RB1 mutation and advanced TNM stage were associated with shorter OS. We identified frequently mutated genes and potential predictors of survival in patients with gastric NECs and MANECs.

3 months ago

Journal • BRCA Biomarker

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • BRCA2 (Breast cancer 2, early onset) • RB1 (RB Transcriptional Corepressor 1) • ARID1A (AT-rich interaction domain 1A) • CCNE1 (Cyclin E1) • LRP1B (LDL Receptor Related Protein 1B) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • CDH1 (Cadherin 1) • RICTOR (RPTOR Independent Companion Of MTOR Complex 2) • GNAS (GNAS Complex Locus) • NFKBIA (NFKB Inhibitor Alpha 2) • SLX4 (SLX4 Structure-Specific Endonuclease Subunit)

HER-2 mutation • LRP1B mutation • RB1 mutation • BRCA2 amplification • KRAS deletion • NOTCH mutation

3ms

Targeting ALDH1A1 to enhance the efficacy of KRAS-targeted therapy through ferroptosis. (PubMed, Redox Biol)

Although the advent of sotorasib and adagrasib, has lifted the "undruggable" stigma of KRAS, the resistance to KRAS inhibitors quickly becomes a major issue. Meanwhile, we established that GTF2I is dephosphorylated at S784 via ERK by KRAS inhibitors, which hinders its nuclear translocation and mediates ALDH1A1's upregulation in response to KRAS inhibitors. In summary, the results offer valuable insights into targeting ALDH1A1 to enhance the effectiveness of KRAS-targeted therapy through ferroptosis in cancer treatment.

3 months ago

Journal

KRAS (KRAS proto-oncogene GTPase) • GPX4 (Glutathione Peroxidase 4) • ALDH1A1 (Aldehyde Dehydrogenase 1 Family Member A1) • CREB1 (CAMP Responsive Element Binding Protein 1)

KRAS deletion

Lumakras (sotorasib) • Krazati (adagrasib)

3ms

Comprehensive genomic sequencing predicts sub-optimal response to bispecific antibodies (BsAb) and chimeric antigen receptor T cells (CAR-T) in multiple myeloma (MM) (IMW 2024)

BsAb and CAR-T may overcome individual standard genomic RF, however harboring multiple genomic RF remains adverse. Clinically available extended genomic characterization predicts response better than FISH alone in this large cohort treated with BsAb/CAR-T. This work will extend into pre-/post-therapy whole genome sequencing for more granular data analysis.

3 months ago

CAR T-Cell Therapy • IO biomarker

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • TNFRSF17 (TNF Receptor Superfamily Member 17)

TP53 mutation • KRAS mutation • NRAS mutation • TP53 mutation + KRAS mutation • KRAS deletion

MSK-IMPACT Heme

3ms

Characterising the genomic landscape of advanced non-squamous NSCLC of Chinese: A territory-wide study in Hong Kong (ESMO Asia 2024)

Providing valuable insights into the mutational landscape of NSCLC. These findings have significant clinical implications in Hong Kong and globally.

3 months ago

Tumor mutational burden • IO biomarker • Metastases

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden)

TP53 mutation • KRAS mutation • EGFR mutation • TMB-H • KRAS G12C • EGFR L858R • HER-2 mutation • EGFR exon 19 deletion • ALK fusion • KRAS G12 • KRAS deletion

FoundationOne® CDx • FoundationOne® Liquid CDx

5ms

Concurrent DNA and RNA NGS Testing to Characterize Rare Fusions in Advanced NSCLC Patients (IASLC-WCLC 2024)

Importantly, co-occurrence of rare fusions and EGFR classical activating mutations in patients pre-treated with anti-EGFR therapy suggests a potential resistance mechanism and consideration of upfront, dual mutation, targeted treatment to improve outcomes. Further clinical studies are needed to validate the best treatment options for these patients with rare fusions.

5 months ago

Clinical • Next-generation sequencing • Metastases

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • NRG1 (Neuregulin 1)

BRAF V600E • KRAS G12C • BRAF V600 • NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • EGFR exon 19 deletion • EGFR T790M • MET exon 14 mutation • ALK fusion • ROS1 fusion • NRG1 fusion • KRAS G12 • BRAF fusion • EGFR fusion • KRAS deletion

Tempus xT Assay

7ms

Circulating tumor DNA and its role in detection, prognosis and therapeutics of hepatocellular carcinoma. (PubMed, Chin J Cancer Res)

This article overviews many conditions in genetic changes linked to the onset and development of HCC, such as dysregulated signaling pathways, somatic mutations, single-nucleotide polymorphisms, and genomic instability. Additionally, efforts are also made to develop treatments for HCC that are molecularly targeted and to unravel some of the genetic pathways that facilitate its early identification.

7 months ago

Journal • Circulating tumor DNA

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CCND1 (Cyclin D1) • KMT2C (Lysine Methyltransferase 2C) • CDK6 (Cyclin-dependent kinase 6) • CCNA2 (Cyclin A2) • AXIN1 (Axin 1) • RASSF1 (Ras Association Domain Family Member 1) • SEPTIN9 (Septin 9)

BRAF mutation • KRAS deletion • RASSF1 methylation

7ms

Protein phosphatase 6 activates NF-κB to confer sensitivity to MAPK pathway inhibitors in KRAS- and BRAF-mutant cancer cells. (PubMed, Sci Signal)

Furthermore, a R264 point mutation in PPP6C conferred loss of function in CRC cells, phenocopying the enhanced NF-κB activation and resistance to MAPK pathway inhibition observed for PPP6C deletion. These findings demonstrate that PP6 constrains the growth of KRAS- and BRAF-mutant cancer cells, implicates the PP6-NF-κB axis as a modulator of MAPK pathway output, and presents a rationale for cotargeting the NF-κB pathway in PPP6C-mutant cancer cells.

7 months ago

Journal

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • CCND1 (Cyclin D1)

KRAS mutation • BRAF mutation • KRAS deletion

8ms

CYRI-B mediated macropinocytosis drives metastasis via lysophosphatidic acid receptor uptake. (PubMed, Elife)

CYRI-B depleted tumour cells show reduced chemotactic responses to lysophosphatidic acid, a major driver of tumour spread, due to impaired macropinocytic uptake of the lysophosphatidic acid receptor-1. Overall, we implicate CYRI-B as a mediator of growth and signaling in pancreatic cancer, providing new insights into pathways controlling metastasis.

8 months ago

Journal

KRAS (KRAS proto-oncogene GTPase) • RAC1 (Rac Family Small GTPase 1)

KRAS deletion

8ms

RAC1-mediated Integrin alpha-6 expression in E-cadherin-deficient gastric cancer cells promotes interactions with the stroma and peritoneal dissemination. (PubMed, Cancer Lett)

These findings indicate that Cdh1 gene loss leads to abnormal expression and changes in the subcellular localization of ITGA6 through RAC1 signalling. The latter, through interactions with CAFs, allows for peritoneal dissemination.

8 months ago

Journal • Stroma

KRAS (KRAS proto-oncogene GTPase) • CDH1 (Cadherin 1) • RAC1 (Rac Family Small GTPase 1) • ITGA6 (Integrin, alpha 6)

KRAS G12 • CDH1 deletion • CDH1 expression • KRAS deletion

8ms

Nardilysin-regulated scission mechanism activates polo-like kinase 3 to suppress the development of pancreatic cancer. (PubMed, Nat Commun)

p41Plk3 phosphorylates c-Fos on Thr164, which in turn induces expression of Plk3 and pro-apoptotic genes. These findings uncover an NRDC-regulated post-translational mechanism that activates Plk3, establishing a prototypic regulation by scission mechanism.

8 months ago

Journal

KRAS (KRAS proto-oncogene GTPase) • FOS (Fos Proto-Oncogene AP-1 Transcription Factor Subunit 2)

KRAS mutation • KRAS G12D • KRAS G12 • KRAS deletion

9ms

The UBE2F-CRL5ASB11-DIRAS2 axis is an oncogene and tumor suppressor cascade in pancreatic cancer cells. (PubMed, Dev Cell)

Collectively, Ube2f or Diras2 plays a tumor-promoting or tumor-suppressive role in the mouse KrasG12D PDAC model, respectively. The UBE2F-CRL5ASB11 axis could serve as a valid target for pancreatic cancer, whereas the levels of UBE2F or DIRAS2 may serve as prognostic biomarkers for PDAC patients.

9 months ago

Journal

KRAS (KRAS proto-oncogene GTPase)

KRAS mutation • KRAS G12D • KRAS G12 • KRAS deletion

pevonedistat (MLN4924)

9ms

Integrated analysis of transcriptome and genome variations in pediatric T cell acute lymphoblastic leukemia: data from north Indian tertiary care center. (PubMed, BMC Cancer)

Overall, the present study demonstrates the frequencies of transcriptomic and genetic alterations from Indian cohort of pediatric T-ALL and is a salient addition to current genomics data sets available in T-ALL.

9 months ago

Journal

KRAS (KRAS proto-oncogene GTPase) • ABL1 (ABL proto-oncogene 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NOTCH1 (Notch 1) • JAK2 (Janus kinase 2) • MTAP (Methylthioadenosine Phosphorylase) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • ETV6 (ETS Variant Transcription Factor 6) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • WT1 (WT1 Transcription Factor) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • JAK3 (Janus Kinase 3) • PHF6 (PHD Finger Protein 6) • SPI1 (Spi-1 Proto-Oncogene) • LPAR6 (Lysophosphatidic Acid Receptor 6) • NKX3-1 (NK3 homeobox 1) • RAG1 (Recombination Activating 1) • TCF7 (Transcription Factor 7)

KRAS mutation • NOTCH1 mutation • CDKN2A deletion • JAK3 mutation • KRAS deletion

9ms

Haploinsufficiency of Adenomatous Polyposis Coli Coupled with Kirsten Rat Sarcoma Viral Oncogene Homologue Activation and P53 Loss Provokes High-Grade Glioblastoma Formation in Mice. (PubMed, Cancers (Basel))

Consequently, our GBM models have proven to be invaluable resources for identifying early disease biomarkers in glioblastoma, as they closely mimic the human disease. The insights gained from these models may pave the way for potential advancements in the diagnosis and treatment of this challenging brain tumor.

9 months ago

Preclinical • Journal

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • GFAP (Glial Fibrillary Acidic Protein)

TP53 mutation • KRAS mutation • TP53 deletion • KRAS deletion

9ms

Albumin promoter-driven FlpO expression induces efficient genetic recombination in mouse liver. (PubMed, Am J Physiol Gastrointest Liver Physiol)

A highly efficient and liver-specific BAC-Alb-FlpO mouse model was developed. In combination with other Cre lines, different genes can be manipulated sequentially in the same cell, or distinct genetic changes can be induced in different cell types of the same organism.

9 months ago

Preclinical • Journal

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • ALB (Albumin)

TP53 mutation • KRAS mutation • KRAS G12D • TP53 deletion • KRAS G12 • KRAS deletion • KRAS expression

9ms

PRMT1 promotes pancreatic cancer development and resistance to chemotherapy. (PubMed, Cell Rep Med)

Pharmacological inhibition of PRMT1 in combination with gemcitabine has a synergistic effect on pancreatic tumor growth in vitro and in vivo. Collectively, our findings implicate PRMT1 as a key regulator of pancreatic cancer development and a promising target for combination therapy.

9 months ago

Journal

KRAS (KRAS proto-oncogene GTPase) • PRMT1 (Protein Arginine Methyltransferase 1)

KRAS deletion

gemcitabine

10ms

5G2 mutant mice model loss of a commonly deleted segment of chromosome 7q22 in myeloid malignancies. (PubMed, Leukemia)

Whereas alkylator exposure modestly accelerated tumor development, the 5G2 deletion did not cooperate with KrasG12D, NrasG12D, or the MOL4070LTR retrovirus in leukemogenesis. 5G2+/del mice are a novel platform for interrogating the role of hemopoietic stem cell attrition/stress, cooperating mutations, genotoxins, and inflammation in myeloid malignancies characterized by monosomy 7/del(7q).

10 months ago

Preclinical • Journal

KRAS (KRAS proto-oncogene GTPase) • CUX1 (cut like homeobox 1)

KRAS G12D • KRAS G12 • NRAS G12 • Chr del(7q) • KRAS deletion

10ms

Molecular and Clinical Characterization of Oncocytic Intraductal Papillary Neoplasms of the Pancreas (USCAP 2024)

The presence of a PRKACA/B fusion appears to contribute to oncocytic morphology, but 71% of fusion-positive cases had mixed epithelial subtypes. Rare cases harbored concurrent fusion and driver mutation associated with IPMN. Though fusion-positive lesions were more commonly seen in the non-recurrence group, they also comprised >50% of cases with disease recurrence.

10 months ago

Clinical

KRAS (KRAS proto-oncogene GTPase) • RNF43 (Ring Finger Protein 43) • SMAD4 (SMAD family member 4) • GNAS (GNAS Complex Locus) • PRKACA (Protein Kinase CAMP-Activated Catalytic Subunit Alpha)

KRAS mutation • RNF43 mutation • SMAD4 deletion • GNAS mutation • KRAS deletion

OncoPanel™ Assay

11ms

Actionable mutations in matched liquid and tissue biopsy next-generation sequencing (ELCC 2024)

Conclusions Importantly, our study highlights the potential of ctDNA in detecting clinically actionable mutations when tumour biopsies are unavailable. Conversely, ctDNA alone is not adequate in reporting TMB.

11 months ago

Tumor mutational burden • Next-generation sequencing • Biopsy

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase)

BRAF V600E • KRAS G12C • BRAF V600 • EGFR L858R • EGFR exon 19 deletion • MET exon 14 mutation • ALK fusion • KRAS G12 • KRAS deletion

FoundationOne® CDx • FoundationOne® Liquid CDx

11ms

CDKN2A-p16 deletion and activated KRAS drive Barrett's-like gland hyperplasia-metaplasia and synergize in the development of dysplasia pre-cancer lesions. (PubMed, Cell Mol Gastroenterol Hepatol)

p16 deletion in LGR5+ cell precursors triggers increased SCJ mucous-gland hyperplasia/metaplasia. KRAS synergizes with p16 deletion resulting in higher grades of SCJ glandular dysplasia, mimicking Barrett's high-grade dysplasia. These genetically modified mouse models establish a functional role of p16 and activated KRAS in the progression of Barrett's like lesions to dysplasia in mice, representing an in vivo model of esophageal pre-cancer. Derived 3D organoid models further provide in vitro modeling opportunities of esophageal pre-cancer stages.

11 months ago

Journal

KRAS (KRAS proto-oncogene GTPase) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • TNFA (Tumor Necrosis Factor-Alpha) • IL1B (Interleukin 1, beta)

CDKN2A deletion • KRAS deletion

11ms

Med23 deficiency reprograms the tumor microenvironment to promote lung tumorigenesis. (PubMed, Br J Cancer)

Collectively, these findings revealed that MED23 may negatively regulate Kras-induced lung tumourigenesis in vivo, which would improve the precise classification of KRAS-mutant lung cancer patients and provide new insights for clinical interventions.

11 months ago

Journal

KRAS (KRAS proto-oncogene GTPase) • CD8 (cluster of differentiation 8) • B2M (Beta-2-microglobulin) • RAS (Rat Sarcoma Virus) • CD4 (CD4 Molecule) • MED23 (Mediator Complex Subunit 23)

KRAS deletion

12ms

KRAS allelic imbalance drives tumour initiation yet suppresses metastasis in colorectal cancer in vivo. (PubMed, Nat Commun)

Importantly, loss of the wild-type allele in aggressive models of KRASG12D-driven CRC significantly alters tumour progression, and suppresses metastasis through modulation of the immune microenvironment. This study highlights the critical role for wild-type Kras upon tumour initiation, progression and therapeutic response in Kras mutant CRC.

12 months ago

Preclinical • Journal

KRAS (KRAS proto-oncogene GTPase)

KRAS G12D • KRAS wild-type • RAS wild-type • KRAS G12 • KRAS deletion

12ms

Whole‑exome sequencing reveals Lewis lung carcinoma is a hypermutated Kras/Nras-mutant cancer with extensive regional mutation clusters in its genome. (PubMed, Sci Rep)

Our data also suggest that LLC is a lung cancer similar to human lung adenocarcinoma. This study lays a molecular basis for the more targeted application of LLC in preclinical research.

12 months ago

Journal

KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)

TP53 mutation • KRAS mutation • NRAS mutation • CDKN2A deletion • KRAS deletion

almost1year

Stiffness-induced cancer-associated fibroblasts are responsible for immunosuppression in a platelet-derived growth factor ligand-dependent manner. (PubMed, PNAS Nexus)

Our data show for the first time that early paracrine signaling leads to profound changes in tissue mechanics, impacting immune responses and tumor progression. Our study highlights that PDGF ligand neutralization can normalize the tissue architecture independent of the genetic background, indicating that finely tuned stromal therapy may open new therapeutic avenues in pancreatic cancer.

almost 1 year ago

Journal

KRAS (KRAS proto-oncogene GTPase) • CD8 (cluster of differentiation 8)

KRAS mutation • KRAS deletion

1year

The HACE1 E3 ligase mediates RAC1-dependent control of mTOR signaling complexes. (PubMed, EMBO Rep)

HACE1 co-localizes with mTOR and RAC1, resulting in RAC1-dependent loss of mTOR protein stability. Together, our data demonstrate that HACE1 destabilizes mTOR by targeting RAC1 within mTOR-associated complexes, revealing a unique ubiquitin-dependent process to control the activity of mTOR signaling complexes.

1 year ago

Journal

KRAS (KRAS proto-oncogene GTPase) • RAC1 (Rac Family Small GTPase 1) • UBR5 (Ubiquitin Protein Ligase E3 Component N-Recognin 5)

KRAS mutation • KRAS deletion • RAC1 deletion • KRAS expression

1year

Evaluation of a real-world clinico-genomics database of patients with upper gastrointestinal (GI) malignancies in Japan. (ASCO-GI 2024)

As part of a nationwide cancer genome screening project, J-SCRUM GI SCREEN database provides comprehensive genomic information for Asian population (Japan). The prevalence of key actionable gene alterations in each tumor type was highly comparable between J-SCRUM GI-SCREEN and TCGA data.

1 year ago

Clinical • Real-world evidence • BRCA Biomarker • Genomic data • Real-world

HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MET (MET proto-oncogene, receptor tyrosine kinase) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NFE2L2 (Nuclear Factor, Erythroid 2 Like 2)

TP53 mutation • KRAS mutation • BRCA2 mutation • BRCA1 mutation • HER-2 amplification • PIK3CA mutation • MET amplification • KRAS G12D • ATM mutation • KRAS G12V • MYC amplification • CDKN2A mutation • ATM deletion • KRAS G12 • NFE2L2 mutation • KRAS deletion

1year

Krüppel-like Factor 5 Plays an Important Role in the Pathogenesis of Chronic Pancreatitis. (PubMed, Cancers (Basel))

Notably, using ChIP-PCR, we showed that KLF5 binds directly to the promoters of Il1b, Il6, and Tgfb1 genes. In summary, the inactivation of Klf5 inhibits ADM and PanIN formation and the development of pancreatic fibrosis.

1 year ago

Journal

KRAS (KRAS proto-oncogene GTPase) • IL6 (Interleukin 6) • TIMP1 (Tissue inhibitor of metalloproteinases 1) • TGFB1 (Transforming Growth Factor Beta 1) • MMP9 (Matrix metallopeptidase 9) • IL1B (Interleukin 1, beta)

KRAS deletion

1year

Comprehensive genomic analysis of cemento-ossifying fibroma. (PubMed, Mod Pathol)

CNAs were detected in 5/11 (45%) cases, with copy gains involving chromosome 12 occurring in 3/11(27%). In conclusion, no recurrent fusions or pathogenic variants have been detected in the present COF cohort, with copy gains involving chromosome 12 occurring in 27% of cases.

1 year ago

Journal • PARP Biomarker

KRAS (KRAS proto-oncogene GTPase) • ATF7IP (Activating Transcription Factor 7 Interacting Protein) • HDAC5 (Histone Deacetylase 5) • APOBEC1 (Apolipoprotein B MRNA Editing Enzyme Catalytic Subunit 1) • CDC73 (Cell Division Cycle 73) • NFIC (Nuclear Factor I C) • PARP2 (Poly(ADP-Ribose) Polymerase 2)

KRAS mutation • KRAS deletion

1year

Prognostic and predictive biomarkers for anti-EGFR monoclonal antibody therapy in RAS wild-type metastatic colorectal cancer: a systematic review and meta-analysis. (PubMed, BMC Cancer)

In RAS wt mCRC patients receiving EGFR-targeted therapy, BRAF mutation is a powerful prognostic and therapy-predictive biomarker, with no effect found for PIK3CA mutation, PTEN mutation or deletion, but the combined biomarker KRAS/NRAS/BRAF/PIK3CA mutations predict resistance to anti-EGFR therapy. Low miR-31-3p expression may have positive prognostic and therapy predictive effects. Evidence on the prognostic and predictive roles of EGFR and its ligands, and HER2/3/4 is insufficient.

1 year ago

Retrospective data • Review • Journal • Metastases

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) • NRAS (Neuroblastoma RAS viral oncogene homolog) • PTEN (Phosphatase and tensin homolog) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • ERBB4 (erb-b2 receptor tyrosine kinase 4) • EREG (Epiregulin) • MIR31 (MicroRNA 31)

KRAS mutation • BRAF mutation • NRAS mutation • PIK3CA mutation • HER-2 expression • PTEN mutation • ERBB3 expression • RAS mutation • RAS wild-type • ERBB3 mutation • PIK3CA mutation + PTEN mutation • AREG expression • ERBB4 expression • KRAS deletion

1year

Development of combination therapies of KRASG12C inhibitor adagrasib in preclinical models of brain metastasis (SNO 2023)

MRTX849 combination therapies with abemaciclib or anti-PD-1 demonstrate intracranial activity, inhibiting BM progression and prolonging survival, in preclinical models of KRASG12C+ BM.

1 year ago

Preclinical • Combination therapy • PD(L)-1 Biomarker • IO biomarker

KRAS (KRAS proto-oncogene GTPase) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)

CDKN2A deletion • KRAS deletion

Verzenio (abemaciclib) • Krazati (adagrasib)

1year

A rapid, multiplex digital PCR assay to detect gene variants and fusions in non-small cell lung cancer. (PubMed, Mol Oncol)

The assay reported an overall 100% positive percent agreement (PPA) and 98.5% negative percent agreement (NPA) compared to a sequencing-based assay in a cohort of 62 human formalin-fixed paraffin-embedded (FFPE) samples. In addition, the dPCR assay rescued actionable information in ten samples that failed to sequence, highlighting the utility of a multiplexed digital PCR assay as a potential reflex solution for challenging NSCLC samples.

1 year ago

Journal

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) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1)

NTRK1 fusion • MET exon 14 mutation • ALK fusion • KRAS deletion

1year

Cell-Free DNA from Blood or Bone Marrow as Alternatives to Bone Marrow Cells for Molecular Diagnostics and Monitoring of Multiple Myeloma (ASH 2023)

PB cfDNA yielded 78% of the aberrations detected in BM-derived PCs, whereas BM cfDNA yielded 62%. The lower rate of detection in BM cfDNA may reflect DNA contamination from dying white blood cells as a result of shipping BM samples in non-cell stabilizing preservative tubes. BM and PB cfDNA contain highly concordant CNV calls to PCs when cfDNA TF estimates were >5%.

1 year ago

Cell-free DNA

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • SDC1 (Syndecan 1) • PRDM1 (PR/SET Domain 1)

BRAF mutation • KRAS deletion

1year

Cancer Genomic Profiling and Minimal Residual Disease Monitoring By Cell-Free DNA Sequencing in Pediatric Leukemia (ASH 2023)

Our study has demonstrated the utility of cfDNA sequencing to identify both sequence and structural somatic mutations in childhood acute leukemia. This approach will be useful to monitor disease, as well as providing a non-invasive diagnostic approach.

1 year ago

Clinical • Minimal residual disease • Cell-free DNA

KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • IKZF1 (IKAROS Family Zinc Finger 1)

IKZF1 deletion • KRAS deletion

1year

Runx3 Restoration Regresses K-Ras-Activated Mouse Lung Cancers and Inhibits Recurrence. (PubMed, Cells)

Runx3 restoration suppressed K-Ras-activated lung cancer mainly through Arf-p53 pathway-mediated apoptosis and partly through p53-independent inhibition of proliferation. This study provides in vivo evidence supporting RUNX3 as a therapeutic tool for the treatment of K-RAS-activated lung cancers with a durable response.

1 year ago

Preclinical • Journal

KRAS (KRAS proto-oncogene GTPase) • RUNX3 (RUNX Family Transcription Factor 3)

KRAS mutation • KRAS G12D • KRAS G12V • RAS mutation • KRAS G12 • KRAS deletion