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Archive - Feb 6, 2020

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Yale Researchers Find That Ubiquitous Cellular Protein, Polycystin 2, When Unmutated, Plays Lead Role In Cell Survival; When Mutated, It Can Cause Polycystic Kidney Disease (PKD)

The protein known as polycystin 2 is present in every cell in the body, but, until now, scientists knew little about its purpose. Yale researchers; together with colleagues at the University of Illinois at Urbana, the Washington University School of Medicine in St. Louis, and Heidelberg University; have discovered that it protects against cell death, making it a potential target for therapies to treat a variety of diseases of the liver and kidneys, as well as for brain aneurysms, heart disease, and cancer. Polycystin 2 (PC2 or TRPP1, formerly TRPP2) is a calcium-permeant transient receptor potential (TRP) cation channel expressed primarily on the endoplasmic reticulum (ER) membrane and primary cilia of all cell and tissue types. The new research on polycystin 2 was reported online on January 15, 2020 in Scientific Reports. The open-access article is titled “Polycystin 2 Is Increased in Disease to Protect Against Stress-Induced Cell Death.” There are over 6 million protein species in the human body, and scientists are still learning the key roles these proteins play. In the case of polycystin 2, researchers had almost exclusively focused on the protein’s role in polycystic kidney disease (PKD), specifically autosomal dominant PKD (AD-PKD), from which the protein draws its name. When polycystin 2 is mutated, it triggers the disease, which is characterized particularly by the development of large, fluid-filled cysts in the kidney, causing renal failure that necessitates a kidney transplant. “No one knew any function for this protein other than when it was mutated,” said Barbara Ehrlich (at left in photo), PhD, Yale Professor of Pharmacology and of Cellular and Molecular Physiology, who co-led the study with graduate student Allison Brill (at right in photo), 2020 Yale Graduate School of Arts & Sciences (GSAS).

Unprecedented Analyses of More Than 2,600 Whole Genome Sequences from 38 Different Tumor Types Results in 21 Studies Published Simultaneously in Nature Journals; One Suggests Many Cancer Mutations Occur Years Before the Cancer Develops

In a virtually unprecedented event, 21 open-access research papers arising from the monumental efforts of the ICGC/TCGA consortium on whole genome sequencing and integrative analysis of cancer have been published simultaneously online on February 5, 2020, in the following journals published by Nature: Nature Communications (8), Nature (6), Nature Genetics (5), Nature Biotechnology (1), and Communications Biology (1). The work is based on an international collaboration of over 1,300 scientists and clinicians from 37 countries known as the Pan-Cancer Analysis of Whole Genomes (PCAWG). The effort involved analysis of more than 2,600 genomes of 38 different tumor types, creating a huge resource of primary cancer genomes. The flagship paper is titled “Pan-Cancer Analysis of Whole Genomes.” In this BioQuick post, another one of the 21 articles (“The Evolutionary History of 2,658 Cancers”) is described. The the titles and links for all 21 articles are provided following description of the Evolutionary History article. In addition, related articles, including editorials and a News & Views article are provided at the end. Researchers at EMBL's European Bioinformatics Institute (EMBL-EBI) and the Francis Crick Institute in the UK have analyzed the whole genomes of over 2r,600 tumors from 38 different cancer types to determine the chronology of genomic changes during cancer development. Cancer occurs as part of a lifelong process in which our genome changes over time. As we age, our cells cannot maintain the integrity of the genome after cell division without making some errors (mutations). This process can be accelerated by various genetic predispositions and environmental factors, such as smoking. Over our lifetimes, these mutations build up and cells may be mis-programmed, leading to cancer.