As recently as a decade ago, we knew virtually nothing about the biology of DIPG tumors. Because biopsies were rarely performed to diagnose DIPG and few families donated tissue following the death of children with DIPG, researchers had little access to DIPG tissue for molecular study. As a result, rather than searching for treatments based on the particulars of DIPG tumors, doctors and researchers treated DIPG on the assumption that the tumor behaved like glioblastoma tumors in adults.
In the last few years, we have seen dramatic advances in the basic research on DIPG tumors. Researchers now have access to DIPG tumor tissue, both because biopsies are becoming more common and because more families are donating the tissue after the child passes away. Researchers have done extensive testing on DIPG tumors – including full genome sequencing – and have identified many mutations and other abnormalities in DIPG tumor cells. Based on this research, we know now that DIPG tumors and adult glioblastoma tumors are almost nothing alike on a cellular level, and so the assumption underlying prior research and clinical studies was incorrect.
In 2012, researchers made a surprising discovery: nearly 80% of DIPG tumors have a mutation in a gene that codes a particular histone protein. Histone proteins are found in the nucleus of the cell. Groups of histones cluster together, and DNA wraps itself around the histones. Because of this relationship, a group of histones is often described as the “spool” around which the DNA “thread” is wound. The way in which DNA wraps itself around histones is important because it can impact which genes are active or inactive in the cell. Because of the histone mutation in DIPG cells, some genes that should be active in normal brain cells are turned off, and those that should be off become active. This discovery was so surprising because histones had never before been identified as playing a role in any type of cancer.
More recent research has shown that not all DIPG tumors are alike. In 2014, researchers identified three different “subgroups” of DIPG tumors, each of which is characterized by a distinct set of gene expression and abnormalities. In addition to the genetic mutations on which the subgroups are based, additional mutations and abnormalities are present in some (but not all) tumors, regardless of which subgroup they are in. These findings have led many researchers and doctors to conclude that developing a single effective treatment for all DIPG patients is unlikely. Instead, an effective treatment plan may need to be tailored to the particular characteristics of each tumor.
Much has been learned about DIPG tumors in the past few years, but many unanswered questions still remain. Researchers continue to study all of the new DIPG tissue that they can obtain with hopes of learning even more about the disease.