Categories
Tag: CDKN2A
Whole-genome sequencing reveals the molecular implications of the stepwise progression of lung adenocarcinoma
Whole-genome sequencing (WGS) analysis of early and advanced adenocarcinomas Whole-genome short read and long read sequencing datasets of 76 lung cancer specimens were analyzed. The datasets included newly generated data for 48 early small-sized lung adenocarcinoma cases (collectively called “Early-Ad” hereafter). These cases included 26 AIS (9 and 17 cases…
Genomic Predictors Associated With Exceptional Response to Systemic Therapy in Advanced Pancreatic Cancer
ABSTRACT Introduction: Exceptional response to therapy is rare in patients with advanced pancreatic cancer. This study explored potential genomic differences between typical and exceptional responses that could confer more favorable biology. Methods: We included exceptional responders and controls with advanced pancreatic cancer from Cleveland Clinic from April 2013 to August…
Single-cell RNAseq reveals the pro-regenerative role of senescent FAPs in muscle regeneration
Abstract Muscle regeneration is associated with transient induction of cellular senescence. However, the role of senescence in muscle regeneration of young mice remains unclear. Using a mouse model deficient in both Cdkn1a and Cdkn2a, we find that a marked reduction in senescent cells correlates with delayed muscle regeneration. Single-cell RNA…
Current Knowledge About The Impact Of Microgravity On Gene Regulation
The effects of a four-day RPM exposure on the human squamous non-small-cell lung cancer cell line CRL-5889 according to Dietz and co-workers [196] (A–D). (A) The RPM exposure leads to partial detachment of cells from the bottom of the flask and after 24 h to first aggregations (spheroid formation) that…
Noncoding mutations cause super-enhancer retargeting resulting in protein synthesis dysregulation during B cell lymphoma progression
B cells undergo a series of programmed genomic alterations that enable the immunoglobulin light and heavy chain loci to generate high-affinity antibodies against invading pathogens. First, B cells undergo variability, diversity and joining (VDJ) recombination in the bone marrow with subsequent somatic hypermutation (SHM) and class switch recombination (CSR) occurring…
Molecular complexity of diffuse large B-cell lymphoma: a molecular perspective and therapeutic implications
Agarwal P, Kabir FM, DeInnocentes P, Bird RC (2012) Tumor suppressor gene p16/INK4A/CDKN2A and its role in cell cycle exit, differentiation, and determination of cell fate. Tumor Suppressor Genes 3(10):27882 Google Scholar Alaggio R, Amador C, Anagnostopoulos I, Attygalle AD, Araujo IBO, Berti E et al (2022) The 5th edition…
Cellular senescence triggers intracellular acidification and lysosomal pH alkalinized via ATP6AP2 attenuation in breast cancer cells
Doxo and Abe promote cellular senescence accompanied by an altered profile of senescence-related genes in breast cancer cells Doxo and Abe were used to treat breast cancer cells (human triple-negative breast cancer cell line MDA-MB-231 and human luminal A subtype breast cancer cell line MCF-7) for 24 h, without a robust…
Identification of Cuproptosis-related circRNA-miRNA-mRNA Network in Laser-induced Choroidal Neovascularization Models and in Peripheral Blood Mononuclear Cells of Patients with Neovascular Age-related Macular Degeneration | Ophthalmic Research
Introduction: To investigate the molecular alterations of cuproptosis-related genes and to construct the cuproptosis-related circRNA-miRNA-mRNA networks in neovascular age-related macular degeneration (nAMD). Methods: The transcriptional profiles of laser-induced choroid neovascularization (CNV) mouse models and nAMD patient samples were obtained from sequencing and from the GEO database (GSE146887), respectively. The expression…
Biomedicines | Free Full-Text | Association between SMAD4 Mutations and GATA6 Expression in Paired Pancreatic Ductal Adenocarcinoma Tumor Specimens: Data from Two Independent Molecularly-Characterized Cohorts
1. Introduction Pancreatic ductal adenocarcinoma (PDAC) has one of the highest case-specific mortality rates of all cancers [1]. Although resection remains the only curative therapy for PDAC, improvements in long-term survival are attributable to advances in systemic treatment [2,3,4,5]. Currently, 5-fluorouracil-based (i.e., with irinotecan and oxaliplatin as FOLFIRINOX) or gemcitabine-based…
[Molecular diagnostics for vitreoretinal lymphoma]
Review doi: 10.1007/s00292-023-01251-z. Online ahead of print. [Article in German] Irina Bonzheim 1 , Julia Salmerón-Villalobos 2 , Daniela Süsskind 3 , Peter Szurman 4 , Florian Gekeler 3 5 , Martin S Spitzer 6 , Itziar Salaverria 2 , Elias Campo 2 , Sarah E Coupland 7 , Leticia Quintanilla-Martinez 8 , Falko Fend 8 Affiliations Expand Affiliations…
Whole genome sequencing in high-grade cervical intraepitheli… : Medicine
1. Introduction Cervical cancer (CC) is the third most common cancer in women worldwide and has a high mortality rate among women. In 2008, CC was responsible for 275,000 deaths, thereby being the fourth leading cause of cancer death in females worldwide.[1,2] In China, CC is the second most…
DIFFERENCES IN MUTATIONAL SIGNATURE OF DIFFUSE LARGE… : HemaSphere
Abstract Topic: 20. Lymphoma Biology & Translational Research Background: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous entity. Recently, the updated World Health Organization classification and The International Consensus Classification have suggested a more subdivided categorization of DLBCL. Moreover, comprehensive molecular subtyping of DLBCL through genetic profiling has broadened…
epialleleR: an R/Bioconductor package for sensitive allele-specific methylation analysis in NGS data | GigaScience
Abstract Low-level mosaic epimutations within the BRCA1 gene promoter occur in 5–8% of healthy individuals and are associated with a significantly elevated risk of breast and ovarian cancer. Similar events may also affect other tumor suppressor genes, potentially being a significant contributor to cancer burden. While this opens a new…
NCT/DKFZ MASTER handbook of interpreting whole-genome, transcriptome, and methylome data for precision oncology
Patient characteristics and tissue context The clinical interpretation of molecular alterations starts with evaluating relevant patient characteristics and the tissue context in which a genetic profile occurs. The former relates, in particular, to previous therapies, in addition to disease stage and clinical performance status. For example, prior targeted therapies warrant…
Multicentric pilot study to standardize clinical whole exome sequencing (WES) for cancer patients
Paired tumor and normal DNA samples from 30 patients were subjected to WES at four ZPM laboratories with subsequent data analysis performed at five ZPM bioinformatic institutions (Fig. 1). DNA was originally derived from fresh-frozen samples that had been analyzed by WES within the multicenter MASTER (Molecularly Aided Stratification for…
Diagnosing and monitoring pancreatic cancer through cell-free DNA methylation: progress and prospects | Biomarker Research
The exploration of methylated biomarkers in plasma for pancreatic cancer is still in its early stages, and the number of studies conducted to date for this purpose is limited. Analysis of cfDNA methylation patterns in pancreatic cancer has been approached both at the whole genome level and by identifying and…
FDA Grants Marketing Authorization to First DNA Test to Assess Genetic Predisposition to Select Cancers
The FDA has granted de novo marketing authorization for the Invitae Common Hereditary Cancers Panel, an in vitro diagnostic test designed to detect genetic variants associated with an elevated risk of developing certain types of cancer.1 Additionally, the panel could also help identify potential cancer-associated variants in patients who have…
KCNQ potassium channels modulate Wnt activity in gastro-oesophageal adenocarcinomas
Introduction The KCNQ (potassium voltage-gated channel subfamily Q) family of ion channels encode potassium transporters (1). KCNQ proteins typically repolarise the plasma membrane of a cell after depolarisation by allowing the export of potassium ions, and are therefore involved in wide-ranging biological functions including cardiac action potentials (2), neural excitability…
Molecular Detection of FGFR2 Rearrangements in Resected Intrahepatic Cholangiocarcinomas: FISH Could Be An Ideal Method in Patients with Histological Small Duct Subtype
Background and aims: Intrahepatic cholangiocarcinoma (ICC) is a subtype of primary liver cancer for which effective therapeutic agents are lacking. Fibroblast growth factor receptor 2 (FGFR2) has become a promising therapeutic target in ICC; however, its incidence and optimum testing method have not been fully assessed. This study investigated the…
Real world evidence reveals improved survival outcomes in biliary tract cancer through molecular matched targeted treatment
Patient characteristics In our analysis, we included patients with biliary tract cancer and available comprehensive molecular characterization data from five Austrian cancer centers. The data cut-off date was September 2022 (Fig. 1). Figure 1 Trial design: Flow chart depicting patient allocation. In total, the molecular profile of 159 patients with biliary…
A biobank of pediatric patient-derived-xenograft models in cancer precision medicine trial MAPPYACTS for relapsed and refractory tumors
Patient characteristics and PDX establishment Between February 2016 and July 2020, 787 pediatric, adolescent and young adult patients with recurrent or refractory malignancies were enrolled in the MAPPYACTS trial;2 756 (96%) patients and their parents consented to the optional ancillary study of preclinical model development (Fig. 1a). 744 patients had a…
Differences in mutational signature of diffuse large B-cell lymphomas according to the primary organ
Background: Comprehensive molecular subtyping of diffuse large B-cell lymphoma (DLBCL) through genetic profiling has broadened our understanding of DLBCL biology. In this study, we investigated whether DLBCL, not otherwise specified (NOS) shows differences in mutational patterns depending on the primary organ. Patients and methods: Panel-based next-generation sequencing was performed on…
DNA/RNA Sequencing Aids Subsequent Treatment Selection in HCC/H-CCK Post Atezolizumab/Bevacizumab
Tissue- and blood-based molecular analysis could help match patients with advanced hepatocellular carcinoma (HCC) or hepatocholangiocarcinoma (H-CCK) following disease progression on frontline atezolizumab (Tecentriq) and bevacizumab (Avastin) to targeted therapy or another TKI based on identified genomic alterations, according to retrospective findings from a single-center study presented at the 2023…
Answer: trajectory-like graph for a data frame
There are better ways to do this than trajectory-type things. In reality, all you need is boxplots or violin plots or whatever grouped by timepoint, optionally split into additional groups if you have other conditions. For example: ![enter image description here][1] [1]: /media/images/c0512668-3fdb-42b6-afe2-fdef4d0f This is split by tissue, grouped by…
Multiparametric senescent cell phenotyping reveals targets of senolytic therapy in the aged murine skeleton
Development and validation of a senescence CyTOF antibody panel We constructed and validated a comprehensive CyTOF antibody panel to include markers for both cell identity and senescent phenotype (Table 1). A defining characteristic of senescent cells is expression of cell cycle inhibitors, in particular p16 or p2129, so we carefully validated…
Molecularly Stratified Treatment Options in Primary Refractory DLBCL/HGBL with MYC and BCL2 or BCL6 Rearrangements (HGBL, NOS with MYC/BCL6)
Alaggio R, Amador C, Anagnostopoulos I, Attygalle AD, Araujo IBO, Berti E, et al. The 5th ediition of the World Health Organization classification of haematolymphoid tumours: lymphoid neoplasms. Leukemia. 2022;36(7):1720–48. doi.org/10.1038/s41375-022-01620-2. Article PubMed PubMed Central Google Scholar Künstner A, Witte HM, Riedl J, Bernard V, Stolting S, Merz H, et…
Genomic characteristics of triple negative apocrine carcinoma: a comparison to triple negative breast cancer
Baseline characteristics We described the baseline clinical and pathological characteristics of TNAC and LK-TNBC in Supplementary Table 1. Only stage at diagnosis was different between TNAC and LK-TNBC (P = 0.03), while no significant differences were observed in other characteristics, including nuclear grade, histologic grade, Ki-67, and status of (neo)adjuvant treatment. Somatic…
Post-operative mortality and recurrence patterns in pancreatic cancer according to KRAS mutation and CDKN2A, p53, and SMAD4 expression
Association of Alterations in Main Driver Genes With Outcomes of Patients With Resected Pancreatic Ductal Adenocarcinoma. Qian ZR, Rubinson DA, Nowak JA, Morales-Oyarvide V, Dunne RF, Kozak MM, Welch MW, Brais LK, Da Silva A, Li T, Li W, Masuda A, Yang J, Shi Y, Gu M, Masugi Y, Bui…
Survival outcomes and relapses in testicular DLBCL
Introduction Primary testicular lymphoma, which accounts for less than 2% of non-Hodgkin lymphoma (NHL) cases, has similarities to extra-nodal NHL that occurs in immune-privileged sites, such as the eye and central nervous system (CNS).1 Pathologically, 80–90% of primary testicular lymphoma cases demonstrate diffuse large B-cell lymphoma (DLBCL) with non-germinal center/activated…
Unveiling the Role of Rb Gene in Prostate Cancer: BET Inhibitors and Immunotherapy
Read the Full Video Transcript Andrea Miyahira: Hi, everyone. I’m Andrea Miyahira and I’m the senior director of global research and scientific communications at PCF. Today I’m joined by Dr. Akash Patnaik, an assistant professor at the University of Chicago Comprehensive Cancer Center. Dr. Patnaik is joining me today to…
Featuring Secura Bio, Genmab, Genentech, Acerta Pharma & Vincerx Pharma
Company Logo Dublin, May 23, 2023 (GLOBE NEWSWIRE) — The “Richter’s Syndrome – Pipeline Insight, 2023” clinical trials has been added to ResearchAndMarkets.com‘s offering. This report provides comprehensive insights about 8+ companies and 10+ pipeline drugs in Richter’s Syndrome pipeline landscape. It covers the pipeline drug profiles, including clinical and…
Rain Oncology’s Phase 3 Data Casts Doubt On Other Trials: Analyst Reevaluate Their Views – Rain Oncology (NASDAQ:RAIN)
Shares of Rain Oncology Inc RAIN recovered in early trading on Tuesday, after having plummeted on disappointing cancer study data. Here are some key analyst takeaways from the company’s decision to halt studies for its lead candidate as a treatment for dedifferentiated (DD) liposarcoma (LPS). Oppenheimer On Rain Oncology Analyst…
Richter’s Syndrome Pipeline Insight Report 2023: Featuring
Dublin, May 23, 2023 (GLOBE NEWSWIRE) — The “Richter’s Syndrome – Pipeline Insight, 2023” clinical trials has been added to ResearchAndMarkets.com‘s offering. This report provides comprehensive insights about 8+ companies and 10+ pipeline drugs in Richter’s Syndrome pipeline landscape. It covers the pipeline drug profiles, including clinical and nonclinical stage…
Rain Oncology Announces Topline Results from Phase 3 MANTRA Trial of Milademetan for the Treatment of Dedifferentiated Liposarcoma
Rain Oncology Inc. – The Phase 3 MANTRA trial did not meet the primary endpoint of progression free survival vs. standard of care – – The median PFS was 3.6 months for milademetan versus 2.2 months for trabectedin with a hazard ratio of 0.89 – – Rain to host a…
Rain Therapeutics Phase 3 MANTRA Trial of Milademetan Did Not Meet its Primary Endpoint By Investing.com
(Updated – May 22, 2023 8:02 AM EDT) Rain Oncology Inc. (NasdaqGS: RAIN), (Rain), a late-stage company developing precision oncology therapeutics with its lead product candidate, milademetan, an oral, small molecule inhibitor of the MDM2-p53 complex that reactivates p53, today announced its topline pivotal Phase 3 MANTRA data. The trial,…
Addressing Skin Cancer: From Screening to Treatment
In the United States (US), The U.S. Preventive Services Task Force (USPSTF) continues to push forth recommendations to stop diseases like skin cancer from developing. However, skin cancer still impacts approximately 9,500 Americans each year, according to the American Academy of Dermatology. According to Meredith McKean, MD, MPH, the USPSTF…
Rain Oncology: Phase 3 Milademetan Data Expected Q2 Of 2023 (NASDAQ:RAIN)
Evgenii Kovalev/iStock via Getty Images Rain Oncology (NASDAQ:RAIN) is a great speculative biotech play to look into. That’s because it is advancing its drug milademetan in several clinical studies. More importantly, it expects to release top line data from its phase 3 MANTRA study using this drug to treat patients…
MYD88L265P and MYD88other variants show different molecular characteristics and prognostic significance in diffuse large B-cell lymphoma
Patient selection and data collection This study retrospectively collected 475 patients diagnosed with de novo DLBCL by two experienced pathologists at the CHCAMS and Suzhou Municipal Hospital from February 6th, 2007 to May 20th, 2022. A total of 132 patients with MYD88 variations were included for analysis. The inclusion criteria…
Convergent genomic diversity and novel BCAA metabolism in intrahepatic cholangiocarcinoma
Multi-omics analyses of the ICC samples Following multiregional sampling of primary ICC cases, we performed multi-omics analyses, including genome, transcriptome, proteome, and metabolome analysis. We used 10 (67 samples), 11 (88 samples), 10 (49 samples) and 10 (49 samples) ICC cases for WES, whole-transcriptome sequencing, proteomic analysis, and metabolomic analysis,…
MUTYH germline mutations in Colombian patients
Lisa Ximena Rodriguez-Rojas,1,2 Estephania Candelo,3,4 Harry Pachajoa,1,2,4 Juan Esteban Garcia-Robledo,3 Jose Antonio Nastasi-Catanese,1,2 Jorge Andres Olave-Rodriguez,2 Angela R Zambrano5 1Department of Human Genetics, Fundación Valle del Lili, Cali, Colombia; 2Faculty of Health Sciences, Universidad Icesi, Cali, Colombia; 3Fundación Valle del Lili, Centro de Investigaciones Clínicas, Cali, Colombia; 4Centro de Investigaciones…
Comprehensive Analysis of circRNA-miRNA-mRNA Network in Cervical Squamous Cell Carcinoma by Integrated Analysis
Introduction Cervical cancer (CC) is one of the most widespread gynaecological cancers that threatens women’s health in developing countries.Citation1 CC progresses through a long stage of precancerous lesions, called cervical intraepithelial neoplasia (CIN), which is classified into three grades: CIN 1, CIN 2 and CIN 3.Citation2 Human papillomaviruses (HPVs) have…
Supplement File from Consistent and Differential Genetic Aberrations between Esophageal Dysplasia and Squamous Cell Carcinoma Detected By Array Comparative Genomic Hybridization
ARTICLE ABSTRACT Purpose: Our aim was to identify frequent genomic aberrations in both esophageal squamous cell carcinoma (ESCC) and esophageal dysplasia and to discover important copy number-driving genes and microRNAs (miRNA) in ESCC.Experimental Design: We conducted array-based comparative genomic hybridization (array CGH) on 59 ESCC resection samples and 16 dysplasia…
Pancreatic adenocarcinomas without KRAS, TP53, CDKN2A and SMAD4 mutations and CDKN2A/CDKN2B copy number alterations: a review of the genomic landscape to unveil therapeutic avenues
Background: Pancreatic adenocarcinoma is one of the cancers with the worst prognosis. The current treatment paradigm based on combination chemotherapy has improved survival over the last decade, but the disease is still fatal in most cases. New therapies exploiting the increasing understanding of the molecular pathology of the disease are…
Expert discusses pros, cons of molecular tests for melanoma
SAN DIEGO – Today’s molecular tests for managing melanoma patients are used to reclassify melanoma, identify patients at risk, as well as for diagnosis, prognosis, and treatment, but each one has its specific applications, benefits, and drawbacks, according to Gregory A. Hosler, MD, PhD. At the annual Cutaneous Malignancy Update,…
FLI1 and FRA1 transcription factors drive the transcriptional regulatory networks characterizing muscle invasive bladder cancer
Sung, H. et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 71, 209–249 (2021). Article PubMed Google Scholar Sanli, O. et al. Bladder cancer. Nat. Rev. Dis. Prim. 3, 17022 (2017). Article PubMed Google Scholar International…
Bioinformatics construction and experimental validation of a cuproptosis-related lncRNA prognostic model in lung adenocarcinoma for immunotherapy response prediction
Data collection and processing The RNA-sequencing data, clinical information and simple nucleotide variation of LUAD patients were retrieved from TCGA database (portal.gdc.cancer.gov/, accessed April 8, 2022). Nineteen cuproptosis-related genes (CRG) were mainly collected from previous study, including LIPT1, GLS, NFE2L2, NLRP3, LIAS, ATP7B, ATP7A, SLC31A1, FDX1, LIPT2, DLD, DLAT, PDHA1,…
Futibatinib Yields Clinical Benefit in FGFR2+ Intrahepatic Cholangiocarcinoma
The covalently binding FGFR1 to 4 inhibitor futibatinib (Lytgobi) achieved measurable clinical benefit in patients with unresectable or metastatic FGFR2 rearranged intrahepatic cholangiocarcinoma, according to findings from the phase 2 FOENIX-CCA2 study (NCT02052778). The objective response rate (ORR) of patients treated with futibatinib was 42% (n = 43/103; 95% CI,…
Rain Oncology receives Buy rating from Roth
Roth Capital Partners renewed coverage of Rain Oncology (Rain Oncology Stock Quote, Charts, News, Analysts, Financials NASDAQ:RAIN) on Tuesday, with Roth analyst Kumaraguru Raja saying there’s a favourable risk-reward on the stock heading into a data readout during the present quarter. Newark, CA-based Rain Oncology is a development stage precision…
Researchers develop new machete technique to slice into cancer genome and study copy number alterations — ScienceDaily
MACHETE is a new CRISPR-based technique developed by researchers at the Sloan Kettering Institute (SKI) to study large-scale genetic deletions efficiently in laboratory models. People are already calling it the Machete Paper. Still, lead authors Francisco “Pancho” Barriga and Kaloyan Tsanov of the Sloan Kettering Institute don’t want the name…
Proscillaridin A induces mitochondrial damage and autophagy in pancreatic cancer and reduces the stability of SMAD4 in Panc-1 cells – Hou
Introduction Pancreatic cancer (PC) is one of the most aggressive and lethal cancers (1). Previous studies have shown that aging, environmental and behavioral changes are more closely related to the dramatic increase in the incidence of PC worldwide than genetic factors (2–5). A position paper published by the European Federation…
BTG2 gene predicts poor outcome in PT-DLBCL
Introduction Primary testicular diffuse large B-cell lymphoma (PT-DLBCL) is a rare and aggressive form of mature B-cell lymphoma.1–3 PT-DLBCL was the most common type of testicular tumor in men aged over 60 and characterized by painless uni- or bilateral testicular masses with infrequent constitutional symptoms.4–6 PT-DLBCL shows significant extranodal tropism,…
A pilot study of the use of dynamic cfDNA from aqueous humor and vitreous fluid for the diagnosis and treatment monitoring of vitreoretinal lymphomas
The diagnosis of vitreoretinal lymphoma (VRL), a rare subtype of primary central nervous system lymphoma (PCNSL), is challenging. We aimed to investigate the mutational landscape of VRL by sequencing circulating tumor DNA (ctDNA) from aqueous humor (AH) and/or vitreous fluid (VF), as well as the application of ctDNA sequencing to…
A genomic mutation spectrum of collecting duct carcinoma in the Chinese population
This article was originally published here BMC Med Genomics. 2022 Jan 3;15(1):1. doi: 10.1186/s12920-021-01143-2. ABSTRACT BACKGROUND: Renal collecting duct carcinoma (CDC) is a rare and lethal subtype of renal cell carcinoma (RCC). The genomic profile of the Chinese population with CDC remains unclear. In addition, clinical treatments are contradictory. In…
Characterization of Blood- Based Molecular Profiling in Pancreatic Adenocarcinoma
Introduction Most cases of pancreatic adenocarcinoma (PDAC) are diagnosed in the metastatic or locally advanced stage. It is the fourth leading cause of cancer death in the United States,1,2 with a 5-year overall survival (OS) around 10% in this country2 despite years of research and therapeutic development. For those patients…
Prognostic Biomarkers Identified for Pancreatic Ductal Adenocarcinoma Using Whole Genome Sequencing
Possible biomarkers for prognosis and clinical outcomes were identified, through the use whole exome sequencing and RNA sequencing, as therapeutic targets for patients with pancreatic ductal adenocarcinoma (PDAC), according to a recent study. The study, published in Therapeutic Advances in Medical Oncology, also reconfirmed genomic landscapes, major driver mutations, and…
Dual Targeting of CDKN2A and PIK3CA May Offer Better Outcomes in Urothelial Carcinoma
Genomic testing varies in the academic and community setting. For community settings, commercial panels are available. However, academic settings have access to tools that provide a more comprehensive views of the genome. Investigators used patient-derived UC organoid (PDO) harboring FGFR3, PIK3CA, and CDKN2A mutations. Dose-response curves of alpelisib (Piqray), abemaciclib…