Genomics

Oncotarget

Oncotarget published this research paper in Volume 13, entitled, "Association of fall rate and functional status by APOE genotype in cancer survivors after exercise intervention" by researchers from Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR; School of Nursing, Oregon Health and Science University, Portland, OR; Department of Radiation Medicine, Oregon Health and Science University, Portland, OR; Department of Radiation Oncology, Dartmouth-Hitchcock’s Dartmouth Cancer Center, Lebanon, NH; Knight Cancer Institute, Oregon Health and Science University, Portland, OR; Department of Neurology and Division of Neuroscience, ONPRC, Oregon Health and Science University, Portland, OR.

DOI - https://doi.org/10.18632/oncotarget.28310

Correspondence to - Jacob Raber - raberj@ohsu.edu

Abstract

Purpose/Objectives: Cancer treatment survivors often report impaired functioning and increased falls. Not all survivors experience the same symptom burden, suggesting individual susceptibilities. APOE genotype is a potential genetic risk factor for cancer treatment related side effects. Lifestyle factors such as physical activity can mitigate the effect of APOE genotype on measures of clinical interest in individuals without a history of cancer. We tested the hypothesis that APOE genotype influences cancer treatment related side effects and symptoms as well as response to exercise intervention.

Materials and Methods: Data from a subsample of a study of fall prevention exercise in post-treatment female cancer survivors aged 50–75 years old (https://clinicaltrials.gov NCT01635413) were used to conduct a secondary data analysis. ApoE genotype was determined by serum sampling. Physical functioning, frequency of falls, and symptom burden were assessed using survey instruments.

Results: Data from 126 female cancer survivors a median of 49 months out from cancer diagnosis were analyzed. ApoE4 carriers trended toward a higher fall rate at baseline (p = 0.059), but after exercise intervention had a fall rate lower than E4 non-carriers both immediately after structured intervention (p = 0.013) and after 6 months of follow up (p = 0.002). E2 carriers did not show improved measures of depressive symptoms and self-report disability after exercise intervention. E3 homozygotes showed increased self report physical activity after the 6 month exercise intervention, but E4 and E2 carriers did not.

Conclusions: APOE genotype may modulate cancer treatment related side effects and symptoms and response to exercise intervention.

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Keywords - apoE, breast cancer, exercise intervention, fall rate, functional status

About Oncotarget

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.

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APOE Genotype Determines Cancer Patients Most Likely to Benefit From Exercise

Aging (Aging-US)

Aging-US published this trending research paper in Volume 14, Issue 21, entitled, "ESR1 dysfunction triggers neuroinflammation as a critical upstream causative factor of the Alzheimer’s disease process" by researchers from NatPro Center, School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Ireland; Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China; Department of Regenerative Medicine, School of Pharmaceutical Sciences, Jilin University, Changchun, China; School of Medicine, Trinity College Dublin, Ireland.

DOI - https://doi.org/10.18632/aging.204359

Corresponding authors - Junying Liu - juliu@tcd.ie 

Abstract

Alzheimer's disease (AD) accounts for approximately 60% of dementia cases worldwide. Advanced age is the most significant risk factor for AD and approximately two-thirds of cases relate to women. While the previous meta-analysis suggests that estrogen receptor (ESR) genetic polymorphisms are closely associated with dementia, the implications of this observation on a molecular level are not entirely understood. Our study explores this intricate molecular puzzle through the use of a variety of bioinformatics tools. Initially, we attempted to elucidate mechanisms underlying breast cancer development by identifying the high-throughput dataset of ESR1-knockdown breast cancer tissue samples. Surprisingly, KEGG pathway enrichment showed that the most frequently occurring proteins were related to axonal guidance and inflammation-related gene markers. These observations were supported by an external high throughput dataset of AD inflammatory samples in vivo. Our results suggest that ESR1 is modulated by apolipoprotein E (APOE) through CEBPB/ATF4, mir-155-5p, or mir-1-3p. Moreover, sea hare-hydrolysates (SHH), as one of the axonal guidance molecules, could regulate the STAT3/PRDM1/CEBPB pathway and consequently induce cell death through pyroptosis signaling pathways, trigger the secretion of IL1β, leading to neuroinflammation and worsening AD pathogenesis. Molecular docking verification demonstrated that the predicted natural products scoulerine and genistein displayed strong binding affinities for BACE1 and ESR1, respectively. This strategy can be used to design novel, personalized therapeutic approaches to treatment and a first-in-class clinical lead for the personalised treatment of AD.

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Keywords - ESR1, Alzheimer’s disease, CEBPB/ATF4, APOE, pyroptosis

About Aging-US

Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways.

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ESR1: A Critical Factor in the Alzheimer’s Disease Process

Oncotarget published this trending research paper in Volume 13, entitled, "Mutation analysis performed on tumor biopsies from patients with newly-diagnosed germinal center aggressive B cell lymphomas" by researchers from the Department of Medicine University of Pennsylvania, Philadelphia, PA.
#openaccess #research #germinalcancer #lymphoma #cancer #oncologyresearch #peerreview #openscience #chemotherapy

DOI - https://doi.org/10.18632/oncotarget.28309

Correspondence to - Daniel J. Landsburg - daniel.landsburg@pennmedicine.upenn.edu 

Abstract

Comprehensive genomic analyses of tumor biopsies from patients with newly-diagnosed germinal center B cell (GCB) diffuse large B cell/high grade B cell lymphoma (DLBCL/HGBL) have identified molecular subtypes predictive of inferior survival, which are characterized by somatic mutations that can be detected through clinical laboratory mutation analysis (CLMA). To determine the frequency and predictive value of individual genetic mutations associated with these experimentally-defined poor-risk subgroups, we reviewed the findings from CLMA performed on tumors from patients with newly-diagnosed GCB DLBCL/HGBL who were previously treated at our institution. CLMA was successfully performed on 58/59 patient tumor biopsies with a median turnaround time of 16 days, and 51 on which CLMA was routinely performed with adequate clinical follow-up were analyzed. Patients whose tumors demonstrated CREBBP mutation experienced a lower estimated rate of 2-year disease free survival (DFS) as compared to those whose tumors did not (45% [95% CI 18–68%] vs. 67% [95% CI 44–83%], P = 0.045). CREBBP mutations may be frequent and predict for inferior DFS in patients with newly-diagnosed GCB DLBCL/HGBL. Furthermore, CLMA may be practically-applied to translate experimental findings into those with more direct application to risk stratification and clinical trial design in subsets of patients with DLBCL/HGBL.

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Press release - https://www.oncotarget.com/news/pr/oncotarget-mutation-analysis-performed-on-tumor-biopsies-from-patients-with-newly-diagnosed-germinal-center-aggressive-b-cell-lymphomas/

Keywords - diffuse large B cell lymphoma, high grade B cell lymphoma, mutation analysis, next generation sequencing, chemotherapy

About Oncotarget

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.

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Mutation Analysis of Newly-Diagnosed Germinal Center Aggressive B Cell Lymphomas

Aging (Aging-US) published this trending research perspective in Volume 14, Issue 20, entitled, “Lamin A to Z in normal aging” by researchers from Independent Affiliation, Lauderhill, FL; The Buck Institute for Research on Aging, Novato, CA; Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore; Centre for Healthy Longevity, National University Health System, Singapore; Departments of Biochemistry and Physiology, Yong Loo Lin School of Medicine, National University of Singapore.
#aging #openaccess #mutation #lifespan #research

DOI - https://doi.org/10.18632/aging.204342

Corresponding author - Brian K. Kennedy - bkennedy@nus.edu.sg 

Abstract

Almost since the discovery that mutations in the LMNA gene, encoding the nuclear structure components lamin A and C, lead to Hutchinson-Gilford progeria syndrome, people have speculated that lamins may have a role in normal aging. The most common HPGS mutation creates a splice variant of lamin A, progerin, which promotes accelerated aging pathology. While some evidence exists that progerin accumulates with normal aging, an increasing body of work indicates that prelamin A, a precursor of lamin A prior to C-terminal proteolytic processing, accumulates with age and may be a driver of normal aging. Prelamin A shares properties with progerin and is also linked to a rare progeroid disease, restrictive dermopathy. Here, we describe mechanisms underlying changes in prelamin A with aging and lay out the case that this unprocessed protein impacts normative aging. This is important since intervention strategies can be developed to modify this pathway as a means to extend healthspan and lifespan.

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Press release - https://www.aging-us.com/news_room/lamin-a-to-z-in-normal-aging

Keywords - lamin A, prelamin A, zmpste24, mTOR, aging

About Aging-US

Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways.

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Aging-US is published by Impact Journals, LLC: http://www.ImpactJournals.com​​

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Paper Spotlight: Lamin A to Z in Normal Aging

Oncotarget published this trending research paper in Volume 13, entitled, "Nectin-4 is widely expressed in head and neck squamous cell carcinoma" by researchers from the Institute of Pathology, University Hospital Bonn (UKB), Bonn, Germany; Department of Otorhinolaryngology, University Medical Center Bonn (UKB), Bonn, Germany; Department of Haemato-oncology, University Hospital Bonn (UKB), Bonn, Germany

DOI - https://doi.org/10.18632/oncotarget.28299

Correspondence to - Glen Kristiansen - glen.kristiansen@ukbonn.de 

Abstract

Purpose: Nectin-4 has been successfully established as a target molecule in locally advanced and metastatic bladder cancer. An antibody-drug conjugate (enfortumab-vedotin) directed against nectin-4 has shown marked tumor remission rates in this tumor type, which is known for high expression rates of nectin-4. As head and neck cancer and urothelial carcinomas share morphological and molecular similarities, we aimed to evaluate Nectin-4 expression in head and neck squamous cell carcinoma (HNSCC).

Material and Methods: A previously described and clinically characterized cohort of HNSCC (n = 159) was analyzed by immunohistochemistry for Nectin-4 expression. The expression data was correlated to clinico-pathological parameters including patient outcome.

Results: Nectin-4 was found in 86.2% of HNSCC, with medium/high expression seen in 32.7% of cases. Non smokers and p16 positive HNSCC showed a higher expression of Nectin-4 (p < 0.005). There was no correlation of Nectin-4 with grading or tumor stage. Nectin-4 positive tumors showed a significant better survival (log rank p = 0.006).

Conclusions: Similar to urothelial carcinoma, Nectin-4 is found in the majority of HNSCC, which clearly warrants further studies to clarify if HNSCC also respond to targeted therapy with enfortumab-vedotin. Moreover, expression of Nectin-4 is associated with HPV infection and may serve as a prognostic marker in HNSCC.

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Keywords - Nectin-4, enfortumab-vedotin, HNSCC, p16

About Oncotarget

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.

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Trending With Impact: Nectin-4 is Widely Expressed in Head and Neck Squamous Cell Carcinoma

Technology Networks

Speaking at The Landscape of Cancer Research 2022 online symposium, Eric Kmiec of the Gene Editing Institute, ChristianaCare, delivered his talk on advances in CRISPR gene editing.

Advancing CRISPR Gene Editing for Solid Tumors Toward Clinical Application

Speaking at The Landscape of Cancer Research 2022 online symposium, Andrea Degasperi of the Early Cancer Institute, University of Cambridge, delivered his talk on mutational signatures discovery and categorization from whole cancer genomes.

Discovering and Categorizing Mutational Signatures From Cancer Whole Genomes

Oxford Nanopore Technologies

Take your sequencing to the next level with the recently released PromethION 2 devices. They enable flexible, high-yield sequencing, in a compact, accessible design. The devices are designed for users with sample processing requirements of up to four full-length sequencing runs per week / ~200 flow cells per year. Each flow cell can deliver hundreds of gigabases of nanopore sequencing data. With this sequencing capacity, you can obtain the data you need for completing large genomes, studying complex metagenomic samples, obtaining known and novel transcripts from single-cell sequencing, and much more.

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Flexible, high-yield nanopore sequencing for every lab

Oncotarget published this trending research perspective in Volume 13, entitled, "FSP1, a novel KEAP1/NRF2 target gene regulating ferroptosis and radioresistance in lung cancers" by researchers from The Institute of Molecular and Translational Medicine, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi’an Jiaotong University, Xi’an 710049, China; Department of Thoracic Surgery, Ruyang People’s Hospital, Luoyang 471200, China; Shaanxi Stem Cell Application Engineering Research Center, Shaanxi Jiuzhou Biomedical Science and Technology Group, Xi’an 710065, China; Department of Thoracic Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, China.

DOI - https://doi.org/10.18632/oncotarget.28301

Correspondence to - Yilei Zhang - zhangyilei@xjtu.edu.cn 

Abstract

In the study of "A targetable CoQ-FSP1 axis drives ferroptosis- and radiation-resistance in KEAP1 inactive lung cancers" which was published earlier in Nature Communications, the authors have identified a novel KEAP1/NRF2 target gene, FSP1, and demonstrated that FSP1 plays an essential role in NRF2-mediated ferroptosis resistance and radioresistance in KEAP1-deficient lung cancer cells. Currently, many NRF2 target genes have been found to participate in the regulation of ferroptosis, and exactly which one plays a dominant role seems unclear. This study proposes that FSP1 is the key effector in NRF2-mediated ferroptosis resistance and radioresistance in KEAP-deficient lung cancer cells, as we discussed in the manuscript.

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Keywords - KEAP1/NRF2, lung cancer, ferroptosis, radioresistance, therapy

About Oncotarget

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.

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