Tag: epigenetics

Possible ‘Central Hub’ Proteins Found in Cancer Cell Growth

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Originally published on Cornerstone, the CHOP Research Blog.

I composed this original article based on an interview with the investigator.

Excerpt:

A study from researchers at The Children’s Hospital of Philadelphia may add new lines to the textbook description of how cancer cells divide uncontrollably and develop into tumors. Their study, published in Nature Communications, identifies and describes an epigenetic mechanism in cancer cells that amplifies the expression of many genes and could be a central hub in cancer cell growth. Unlike most molecular cancer discoveries that advance knowledge of the disease by dividing it into narrower subtypes, this finding could directly apply to multiple cancer types.

“We know the signaling pathway known as the Rb pathway is altered in pretty much every single tumor that you can find in clinical settings,” said Patrick Viatour, PharmD, PhD, the study’s senior author, an investigator at CHOP and assistant professor of Pathology and Laboratory Medicine at the Perelman School of Medicine at the University of Pennsylvania.

Dr. Viatour’s research focuses on a family of proteins in the Rb pathway, called E2f transcription factors, that are an important part of the process of cell division — the cell cycle of reproduction that is carefully controlled in healthy cells but proceeds out of control when cancer cells proliferate. Transcription factors, including the E2f family of proteins, bind to specific target regions of DNA and help to either activate or deactivate expression of certain genes.

As a result of Rb pathway alteration, E2f factors are steadily turned on in cancer. In the study primarily using a mouse model of liver cancer, Dr. Viatour and his team found that E2f1 progressively accumulates as cancer progresses.

On the Trail of a Cancer Predisposition Syndrome

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Originally published in Bench to Bedside, the CHOP Research monthly publication

I composed this original article and complementary blog post based on interviews with the investigator and two parents of children with this syndrome.

Excerpt:

Inside the cells of a developing human embryo is a little piece of “Alice in Wonderland.” While most of our bodies’ genes are expressed from both our mothers’ and fathers’ chromosomes, there is a particular growth-regulating region of chromosome 11 where Dad’s genes make you grow bigger, and Mom’s genes make you small. As in Alice’s adventure, there is potential for some difficult situations to occur when that growth process is not handled with exacting care.

With new grants awarded by the St. Baldrick’s Foundation and the National Cancer Institute, attending physician and geneticist Jennifer M. Kalish, MD, PhD, at The Children’s Hospital of Philadelphia, is going down the rabbit hole to try to set things right. She aims to answer key questions about cancer while helping children with Beckwith-Wiedemann Syndrome (BWS), an overgrowth disorder that can result when epigenetic regulation of growth-regulating regions of chromosome 11 goes awry.

Five Fascinating Facets of Beckwith-Wiedemann Syndrome

Originally published on Cornerstone, the CHOP Research Blog

I composed this blog post as a complement to the above article about the new investigation into BWS.

Excerpt:

1. BWS is a mosaic condition. Some cells and organs or limbs grow unusually large in children with BWS, and some do not. Patterns of this overgrowth vary from child to child. This mosaicism happens because the changes in gene expression that cause BWS arise early when the developing human embryo has relatively few cells — and the changes occur in only some of them. Cells and organs descended from those dysregulated cells have unusual growth patterns, while cells and organs descended from normally developing cells continue to grow at normal rates. This results in a widely varying presentation of the syndrome in different children.

The mosaic nature of the condition makes it challenging to manage the elevated cancer risk that goes along with BWS. As Dr. Kalish noted, “I can see if a child’s arms are bigger. I cannot see what is going on in the liver or kidney.” Each child’s areas of overgrowth are variable, so all young children with BWS must undergo regular cancer screenings.