Chromosomal translocation

Narcolepsy type 1 (NT1) is a rare disease characterized by severe drowsiness, cataplexy, hypnagogic hallucinations, sleep paralysis, poor night sleep, and often obesity. NT1 is caused by irreversible loss of orexin (ORX)/hypocretin neurons in the lateral hypothalamus with decreased ORX levels in the cerebrospinal fluid (CSF). Although the underlying process leading to this destruction remains unclear; an autoimmune origin is suspected.
The study authors recently compared the bacterial communities of the fecal microbiota of NT1 patients and control subjects. Initial results demonstrated a difference in overall bacterial community structure in NT1 compared to controls, as assessed by beta diversity, even after adjusting for body mass index (BMI). The Shannon biodiversity index was also correlated with the duration of NT1 disease. However, no association was found between the structure of the microbial community and the clinical characteristics of NT1 patients.
In 2022, a second study from the SOMNOBANK cohort on a larger population confirmed these results, showing dysbiosis between NT1 patients and the control population. The altered intestinal microbial diversity supports the important role of the environment in the development and pathogenesis of NT1. Other studies have established a link between dysbiosis, intestinal permeability and inflammation in other neuroimmune pathologies. Currently, no study has focused on these phenomena of bacterial translocation, intestinal permeability and immune activation linked to the microbiota in type 1 narcolepsy patients.
The study hypothesis is that NT1 patients with dysbiosis in their intestinal microbiota also present a bacterial translocation with an intestinal origin, leading to a systemic inflammatory syndrome favoring an autoimmune damage destroying hypocretin neurons in the hypothalamus. The study authors suspect that microbial elements (DNA) involved in the autoimmune process could be detected in the CSF. This bacterial translocation could vary over time depending on: i) the progression of the disease and its management; ii) changing dysbiosis and: iii) the increase in intestinal permeability and inflammation.

Venetoclax is considered as a promising agent for light-chain (AL) amyloidosis due to the high percentage of t(11;14). Several retrospective studies showed venetoclax-based therapy could induce rapid and profound hematologic response in AL patients with favorable safety profile. As an oral agent with encouraging data, it is worth to prospectively evaluate the efficacy and safety of venetoclax in untreated AL amyloidosis patients.

Microphthalmia transcription factor (MiT) family translocation renal cell carcinomas (TRCC) are rare subtypes of kidney cancers, which often arise in children and young adults. TRCC are characterized by translocations affecting transcription factors: Transcription Factor Binding To Immunoglobulin Heavy Constant Mu Enhancer 3 (TFE3) and Transcription Factor EB (TFEB). Little is known about TRCC molecular heterogeneity, in particular their transcriptomic and epigenetic subtype classification. Clinical behavior of TRCC is varying with age and Tumor, Node, Metastasis (TNM) stage. However, the biological basis of this aggressiveness is poorly understood.
PURPOSE: The primary goal of this study is to decipher specific alterations in aggressive TRCC, defined as cases with metastatic dissemination at diagnosis. To tackle this problem, a retrospective cohort of TRCC cases in children and young adults will be created. We will then perform integrative comprehensive multi-omics analysis of these tumors to identify genetic, epigenetic and immune biomarkers associated with metastatic behavior in a training and validation datasets. Comparison of the multi-omics data will be compared to other type of rare Kidney tumors as well as clear-cell renal cell carcinomas