Circulating tumor DNA validity and potential uses in metastatic breast cancer.

Following the first characterization of circulating tumor DNA (ctDNA) in the 1990s, recent advances led to its introduction in the clinics. At present, the European Society Of Medical Oncology (ESMO) recommendations endorse ctDNA testing in routine clinical practice for tumor genotyping to direct molecularly targeted therapies in patients with metastatic cancer. In studies on metastatic breast cancer, ctDNA has been utilized for treatment tailoring, tracking mechanisms of drug resistance, and for predicting disease response before imaging. We review the available evidence regarding ctDNA applications in metastatic breast cancer.

Recent Developments in Diagnostic and Prognostic Biomarkers for Colorectal Cancer: A Narrative Review.

BACKGROUND: Colorectal cancer was reported as the second most common cause of cancer death worldwide, in the year 2020. This disease is an important public health problem considering its high incidence and mortality rates. SUMMARY: The molecular events that lead to colorectal cancer include genetic and epigenetic abnormalities. Some of the most important molecular mechanisms involved include the APC/ß-catenin pathway, the microsatellite pathway, and the CpG island hypermethylation. Evidence in the literature supports a role for the microbiota in the development of colon carcinogenesis, and specific microbes may contribute to or prevent carcinogenesis. Progress in prevention, screening, and management has improved the overall prognosis of the disease when diagnosed at an early stage; yet metastatic disease continues to have a poor long-term prognosis due to late-stage diagnosis and treatment failure. Biomarkers are a key tool for early detection and prognosis and aim to reduce morbidity and mortality associated with colorectal cancer. The main focus of this narrative review is to provide an update on the recent development of diagnostic and prognostic biomarkers in stool, blood, and tumor tissue samples. KEY MESSAGES: The review focuses on recent investigations in microRNAs, cadherins, Piwi-interacting RNAs, circulating cell-free DNA, and microbiome biomarkers which can be applied for the diagnosis and prognosis of colorectal cancer.

Genome-wide association studies reveal shared genetic haplotypes of autoimmune rheumatic and endocrine diseases with psychiatric disorders.

BACKGROUND: Several studies have shown that autoimmune diseases are associated with psychiatric diseases like depression and psychosis. Genetic evidence supports this association. The aim of this study was to investigate if genetic variants predisposing to autoimmune diseases and psychiatric disorders are genetically linked, constructing the common haplotypes. METHODS: All registered single nucleotide polymorphisms (SNPs) in the Genome-wide association studies ("GWAS catalog") having been associated with autoimmune rheumatic and endocrine diseases were investigated for being in linkage disequilibrium with any psychiatric disorders' associated SNPs. Analysis was performed by the LDtrait and LDhap bioinformatics tools. RESULTS: Multiple chromosomal regions have been detected containing rheumatic/endocrine diseases' predisposing SNPs and psychiatric disorders' predisposing SNPs. The genetic haplotypes have been constructed for some of these genetic regions. Six of the autoimmune rheumatic and endocrine diseases examined here share a common haplotype with psychiatric diseases at the HLA locus 6p21-22. CONCLUSION: Our study shows that autoimmune diseases and psychiatric diseases are genetically linked. Genetic haplotypes have been constructed, showing in detail this genetic linkage.

COVID-19 vaccine safety during pregnancy in women with systemic lupus erythematosus.

COVID-19 vaccination has been shown to be safe in patients with systemic lupus erythematosus (SLE), but data on vaccine-associated adverse events (AEs) during the antenatal and lactation period are scarce or lacking. We investigated COVID-19 vaccination-related AEs in pregnant SLE patients from the COVAD study, a global esurvey involving 157 collaborators from 106 countries. A total of 9201 complete responses were extracted. Among 6787 (73.8%) women, we identified 70 (1.1%) who were exposed to at least one COVID-19 vaccine dose during pregnancy, 11 with SLE. Delayed onset (>7 days) vaccine-related AEs were triangulated with disease activity, treatment changes due to flare after vaccination, and COVID-19 infections in vaccinated pregnant women. Health-related quality of life and physical function was recorded using PROMIS. Age of patients ranged from 28 to 39 years; 5/11 women were of Asian origin. None of these patients reported major vaccine AEs or change in the status of their autoimmune disease. Although minor AEs were common, they did not impair daily functioning, and the symptoms resolved after a median of 3 (IQR: 2.5-5.0) days. All patients reported good to excellent health status. No adverse pregnancy outcomes were reported. Importantly, none of the patients reported thrombotic events post-vaccination, which provides reassurance in a patient population with a high risk for cardiovascular comorbidity and thrombosis, especially in the presence of antiphospholipid antibodies or the antiphospholipid syndrome, a considerable portion of SLE patients. Our findings provide reassurance and can contribute to informed decisions regarding vaccination in patients with SLE and high-risk pregnancies due to their background autoimmune disease. The risk/benefit ratio of COVID-19 vaccination appears favourable, with vaccines both providing passive immunisation to the fetus and active immunisation to the mother with no signals of exacerbation of the mother's autoimmune disease.

The Role of TP53 in Adaptation and Evolution.

The TP53 gene is a major player in cancer formation, and it is considered the most important tumor suppressor gene. The p53 protein acts as a transcription factor, and it is involved in DNA repair, senescence, cell-cycle control, autophagy, and apoptosis. Beyond cancer, there is evidence that TP53 is associated with fertility, aging, and longevity. Additionally, more evidence exists that genetic variants in TP53 are associated with environmental adaptation. Special TP53 amino-acid residues or pathogenic TP53 mutations seem to be adaptive for animals living in hypoxic and cold environments or having been exposed to starvation, respectively. At the somatic level, it has recently been proven that multiple cancer genes, including TP53, are under positive selection in healthy human tissues. It is not clear why these driver mutations do not transform these tissues into cancerous ones. Other studies have shown that elephants have multiple TP53 copies, probably this being the reason for the very low cancer incidence in these large animals. This may explain the famous Peto's paradox. This review discusses in detail the multilevel role of TP53 in adaptation, according to the published evidence. This role is complicated, and it extends from cells to individuals and to populations.