Fred Hutchinson Cancer Research Center

About: Fred Hutchinson Cancer Research Center is a nonprofit organization based out in Cape Town, South Africa. It is known for research contribution in the topics: Population & Transplantation. The organization has 12322 authors who have published 30954 publications receiving 2288772 citations. The organization is also known as: Fred Hutch & The Hutch.

Clinical characteristics of different histologic types of breast cancer.

Abstract: Breast cancer is a heterogeneous disease, though little is known about some of its rarer forms, including certain histologic types. Using Surveillance, Epidemiology, and End Results Program data on 135 157 invasive breast cancer cases diagnosed from 1992 to 2001, relationships between nine histologic types of breast cancer and various tumour characteristics were assessed. Among women aged 50–89 years at diagnosis, lobular and ductal/lobular carcinoma cases were more likely to be diagnosed with stage III/IV, ⩾5.0 cm, and node-positive tumours compared to ductal carcinoma cases. Mucinous, comedo, tubular, and medullary carcinomas were less likely to present at an advanced stage. Lobular, ductal/lobular, mucinous, tubular, and papillary carcinomas were less likely, and comedo, medullary, and inflammatory carcinomas were more likely to be oestrogen receptor (ER) negative/progesterone receptor (PR) negative and high grade (notably, 68.2% of medullary carcinomas were ER−/PR− vs 19.3% of ductal carcinomas). In general, similar differences were observed among women diagnosed at age 30–49 years. Inflammatory carcinomas are associated with more aggressive tumour phenotypes, and mucinous, tubular, and papillary tumours are associated with less aggressive phenotypes. The histologic types of breast cancer studied here differ greatly in their clinical presentations, and the differences in their hormone receptor profiles and grades point to their likely different aetiologies.

The 4D nucleome project

Abstract: The 4D Nucleome Network aims to develop and apply approaches to map the structure and dynamics of the human and mouse genomes in space and time with the goal of gaining deeper mechanistic insights into how the nucleus is organized and functions. The project will develop and benchmark experimental and computational approaches for measuring genome conformation and nuclear organization, and investigate how these contribute to gene regulation and other genome functions. Validated experimental technologies will be combined with biophysical approaches to generate quantitative models of spatial genome organization in different biological states, both in cell populations and in single cells.

Turnover of cyclin E by the ubiquitin-proteasome pathway is regulated by cdk2 binding and cyclin phosphorylation.

Abstract: Cyclin E is a mammalian G1 cyclin that is both required and rate limiting for entry into S phase. The expression of cyclin E is periodic, peaking at the G1-S transition and then decaying as S phase progresses. To understand the mechanisms underlying cyclin E periodicity, we have investigated the regulation of cyclin E degradation. We find that cyclin E is degraded by the ubiquitin-proteasome system, and that this degradation is regulated by both cdk2 binding and cdk2 catalytic activity. Free cyclin E is readily ubiquitinated and degraded by the proteasome. Binding to cdk2 protects cyclin E from ubiquitination, and this protection is reversed by cdk2 activity in a process that involves phosphorylation of cyclin E itself. The data are most consistent with a model in which cdk2 activity initiates cyclin E degradation by promoting the disassembly of cyclin E-cdk2 complexes, followed by the ubiquitination and degradation of free cyclin E.