Peripheral blood DNA methylation predicts the early onset of primary tumor in TP53 mutation carriers.

Li-Fraumeni syndrome (LFS) confers high lifetime cancer risk due to germline TP53 pathogenic variants (PV). A comprehensive surveillance regimen termed the 'Toronto Protocol', has been adopted for early tumor detection, demonstrating improved survival among TP53 PV carriers. However, the protocol's "one-size-fits-all" approach fails to consider individual cancer risk.

Advancing cancer research via comparative oncology.

In the ongoing battle against cancer, the natural world provides promising inspiration for designing novel therapeutic strategies. The field of comparative oncology offers a valuable source of such inspiration. By combining evolutionary biology, ecology, veterinary medicine and clinical oncology, comparative oncology aims to better understand cancer, especially by highlighting taxa that are strongly resistant or susceptible to cancer and to identify the molecular and cellular mechanisms underlying the remarkable cancer resistance of some taxa.

Germline Pathogenic DROSHA Variants Are Linked to Pineoblastoma and Wilms Tumor Predisposition.

Purpose: DROSHA, DGCR8, and DICER1 regulate miRNA biogenesis and are commonly mutated in cancer. Although DGCR8 and DICER1 germline pathogenic variants (GPV) cause autosomal dominant tumor predisposition, no association between DROSHA GPVs and clinical phenotypes has been reported.

Experimental Design: After obtaining informed consent, sequencing was performed on germline and tumor samples from all patients.

Disparities in childhood leukemia survival for Asian, Native Hawaiian, and Pacific Islanders in the United States.

While some previous studies disaggregated the Asian, Native Hawaiian, and Pacific Islander (ANHPI) population to investigate survival for childhood leukemia, further studies are needed to understand the differences between subpopulations. The aim of our study was to estimate 5-year relative survival for patients with childhood leukemia and to investigate disparities in prognostic factors with disaggregation of the ANHPI population. We used the Surveillance, Epidemiology, and End Results Program 17 database and included 1881 ANHPI patients with childhood leukemia and 8772 non-Hispanic White (NHW) patients with childhood leukemia.

DNA repair and anti-cancer mechanisms in the long-lived bowhead whale.

At over 200 years, the maximum lifespan of the bowhead whale exceeds that of all other mammals. The bowhead is also the second-largest animal on Earth, reaching over 80,000 kg. Despite its very large number of cells and long lifespan, the bowhead is not highly cancer-prone, an incongruity termed Peto's Paradox.

Uptake of Cancer Genetic Services for Chatbot vs Standard-of-Care Delivery Models: The BRIDGE Randomized Clinical Trial.

Importance: Increasing numbers of unaffected individuals could benefit from genetic evaluation for inherited cancer susceptibility. Automated conversational agents (ie, chatbots) are being developed for cancer genetics contexts; however, randomized comparisons with standard of care (SOC) are needed.

Objective: To examine whether chatbot and SOC approaches are equivalent in completion of pretest cancer genetic services and genetic testing.

Germline mutation rate predicts cancer mortality across 37 vertebrate species.

Background And Objectives: Cancer develops across nearly every species. However, cancer occurs at unexpected and widely different rates throughout the animal kingdom. The reason for this variation in cancer susceptibility remains an area of intense investigation.

User experience of a family health history chatbot: A quantitative analysis.

Objective: Family health history (FHx) is an important tool in assessing one's risk towards specific health conditions. However, user experience of FHx collection tools is rarely studied. ItRunsInMyFamily.

Germline Genetic Testing and Survival Outcomes Among Children With Rhabdomyosarcoma: A Report From the Children's Oncology Group.

Importance: Determining the impact of germline cancer-predisposition variants (CPVs) on outcomes could inform novel approaches to testing and treating children with rhabdomyosarcoma.

Objective: To assess whether CPVs are associated with outcome among children with rhabdomyosarcoma.

Design, Setting, And Participants: In this cohort study, data were obtained for individuals, aged 0.

Evolutionary determinants of curability in cancer.

The emergence of drug-resistant cells, most of which have a mutated TP53 gene, prevents curative treatment in most advanced and common metastatic cancers of adults. Yet, a few, rarer malignancies, all of which are TP53 wild type, have high cure rates. In this Perspective, we discuss how common features of curable cancers offer insights into the evolutionary and developmental determinants of drug resistance.

Cancer Prevalence Across Vertebrates.

Cancer is pervasive across multicellular species, but what explains differences in cancer prevalence across species? Using 16,049 necropsy records for 292 species spanning three clades (amphibians, sauropsids and mammals) we found that neoplasia and malignancy prevalence increases with adult weight (contrary to Peto's Paradox) and somatic mutation rate, but decreases with gestation time. Evolution of cancer susceptibility appears to have undergone sudden shifts followed by stabilizing selection. Outliers for neoplasia prevalence include the common porpoise (<1.

TP53 germline pathogenic variant frequency in anaplastic rhabdomyosarcoma: A Children's Oncology Group report.

Rhabdomyosarcoma (RMS) is a well-described cancer in Li-Fraumeni syndrome, resulting from germline TP53 pathogenic variants (PVs). RMS exhibiting anaplasia (anRMS) are associated with a high rate of germline TP53 PVs. This study provides updated estimates of the prevalence of TP53 germline PVs in RMS (3%) and anRMS (11%) from a large cohort (n = 239) enrolled in five Children's Oncology Group (COG) clinical trials.

Li-Fraumeni Syndrome-Associated Dimer-Forming Mutant p53 Promotes Transactivation-Independent Mitochondrial Cell Death.

Unlabelled: Cancer-relevant mutations in the oligomerization domain (OD) of the p53 tumor suppressor protein, unlike those in the DNA binding domain, have not been well elucidated. Here, we characterized the germline OD mutant p53(A347D), which occurs in cancer-prone Li-Fraumeni syndrome (LFS) patients. Unlike wild-type p53, mutant p53(A347D) cannot form tetramers and exists as a hyperstable dimeric protein.

Corrigendum: Neonatal NET-Inhibitory Factor improves survival in the cecal ligation and puncture model of polymicrobial sepsis by inhibiting neutrophil extracellular traps.

[This corrects the article DOI: 10.3389/fimmu.2022.

NETosis induction reflects COVID-19 severity and long COVID: insights from a 2-center patient cohort study in Israel.

Background: COVID-19 severity and its late complications continue to be poorly understood. Neutrophil extracellular traps (NETs) form in acute COVID-19, likely contributing to morbidity and mortality.

Objectives: This study evaluated immunothrombosis markers in a comprehensive cohort of acute and recovered COVID-19 patients, including the association of NETs with long COVID.

Elephant TP53-RETROGENE 9 induces transcription-independent apoptosis at the mitochondria.

Approximately 20 TP53 retrogenes exist in the African and Asian elephant genomes (Loxodonta Africana, Elephas Maximus) in addition to a conserved TP53 gene that encodes a full-length protein. Elephant TP53-RETROGENE 9 (TP53-R9) encodes a p53 protein (p53-R9) that is truncated in the middle of the canonical DNA binding domain. This C-terminally truncated p53 retrogene protein lacks the nuclear localization signals and oligomerization domain of its full-length counterpart.

Neonatal NET-Inhibitory Factor improves survival in the cecal ligation and puncture model of polymicrobial sepsis by inhibiting neutrophil extracellular traps.

Introduction: Neutrophil extracellular traps (NETs) clear pathogens but may contribute Q8 pathogenically to host inflammatory tissue damage during sepsis. Innovative therapeutic agents targeting NET formation and their potentially harmful collateral effects remain understudied.

Methods: We investigated a novel therapeutic agent, neonatal NET-Inhibitory Factor (nNIF), in a mouse model of experimental sepsis - cecal ligation and puncture (CLP).

Heritable defects in telomere and mitotic function selectively predispose to sarcomas.

Cancer genetics has to date focused on epithelial malignancies, identifying multiple histotype-specific pathways underlying cancer susceptibility. Sarcomas are rare malignancies predominantly derived from embryonic mesoderm. To identify pathways specific to mesenchymal cancers, we performed whole-genome germline sequencing on 1644 sporadic cases and 3205 matched healthy elderly controls.

Germline TP53 mutations undergo copy number gain years prior to tumor diagnosis.

Li-Fraumeni syndrome (LFS) is a hereditary cancer predisposition syndrome associated with germline TP53 pathogenic variants. Here, we perform whole-genome sequence (WGS) analysis of tumors from 22 patients with TP53 germline pathogenic variants. We observe somatic mutations affecting Wnt, PI3K/AKT signaling, epigenetic modifiers and homologous recombination genes as well as mutational signatures associated with prior chemotherapy.

Collaboration to Promote Research and Improve Clinical Care in the Evolving Field of Childhood Cancer Predisposition.

Germline pathogenic variants in cancer susceptibility genes are identified in up to 18% of all children with cancer. Because pediatric cancer predisposition syndromes (CPS) themselves are rare and underrecognized, there are limited data to guide the diagnosis and management of affected children and at-risk relatives. Furthermore, the care of affected children requires distinct considerations given the early onset of cancers, lifelong risks of additional cancers, and potential late effects of therapy.

Of Elephants and Other Mammals: A Comparative Review of Reproductive Tumors and Potential Impact on Conservation.

Reproductive tumors can impact conception, pregnancy, and birth in mammals. These impacts are well documented in humans, while data in other mammals are limited. An urgent need exists to understand the reproductive impact of these lesions in endangered species, because some endangered species have a documented high prevalence of reproductive tumors.