1. PI3Kδ and primary immunodeficiencies
Sergey Nejentsev, Klaus Okkenhaug, Alison M Condliffe, Carrie L Lucas, Anita Chandra Nat Rev Immunol . 2016 Nov;16(11):702-714. doi: 10.1038/nri.2016.93.
Primary immunodeficiencies are inherited disorders of the immune system, often caused by the mutation of genes required for lymphocyte development and activation. Recently, several studies have identified gain-of-function mutations in the phosphoinositide 3-kinase (PI3K) genes PIK3CD (which encodes p110δ) and PIK3R1 (which encodes p85α) that cause a combined immunodeficiency syndrome, referred to as activated PI3Kδ syndrome (APDS; also known as p110δ-activating mutation causing senescent T cells, lymphadenopathy and immunodeficiency (PASLI)). Paradoxically, both loss-of-function and gain-of-function mutations that affect these genes lead to immunosuppression, albeit via different mechanisms. Here, we review the roles of PI3Kδ in adaptive immunity, describe the clinical manifestations and mechanisms of disease in APDS and highlight new insights into PI3Kδ gleaned from these patients, as well as implications of these findings for clinical therapy.
2. Genomic landscape of colorectal carcinogenesis
Jin Cheon Kim, Walter F Bodmer J Cancer Res Clin Oncol . 2022 Mar;148(3):533-545. doi: 10.1007/s00432-021-03888-w.
Purpose:The molecular pathogenesis of solid tumour was first assessed in colorectal cancer (CRC). To date, ≤ 100 genes with somatic alterations have been found to inter-connectively promote neoplastic transformation through specific pathways. The process of colorectal carcinogenesis via genome landscape is reviewed on the basis of an adenoma-to-carcinoma sequence, as shown by serial histological and epidemiological observations.Methods:The relevant literatures from PubMed (1980-2021) have been reviewed for this article.Results:The major routes of CRC development, chromosomal instability (CIN), microsatellite instability (MSI), and the serrated route either via CIN or MSI, proceed through the respective molecular pathway of colorectal carcinogenesis. Particular aspects of CRC carcinogenesis can also be determined by evaluating familial CRCs (FCRC) and genotype-phenotype correlations. Specific causative gene alterations still leave to be identified in several FCRCs. Otherwise, recently verified FCRC can be particularly notable, for example, EPCAM-associated Lynch syndrome, polymerase proofreading-associated polyposis, RNF43-associated polyposis syndrome or NTHL1 tumour syndrome, and hereditary mixed polyposis syndrome. The oncogenic landscape is described, including representative pathway genes, the three routes of carcinogenesis, familial CRCs, genotype-phenotype correlations, the identification of causative genes, and consensus molecular subtypes (CMS).Conclusion:Whole genome research using multi-gene panels (MGPs) has facilitated high through-put detection of previously unidentified genes involved in colorectal carcinogenesis. New approaches designed to identify rare variants are recommended to consider their alterations implicated in the molecular pathogenesis.
3. Meningococcal immunology
Patricia A Hughes, Martha L Lepow Immunol Allergy Clin North Am . 2003 Nov;23(4):769-86. doi: 10.1016/s0889-8561(03)00092-4.
There is a major need for an effective vaccine against serogroup B disease. The long-term efficacy of the serogroups A, C, Y and W135 conjugate vaccines and the need for booster vaccines has to be determined, as does the effect of changing epidemiology in the United States and worldwide. Control of serogroup A disease in sub-Saharan Africa is a major challenge.
