Additional presentations of note at this year's American Association for Cancer Research Annual Meeting:
Reclassifying low-grade brain tumors
According to findings presented by Roel Verhaak, Ph.D. assistant professor of Bioinformatics and Computational Biology, comprehensive genomic analysis of low-grade brain tumors allows them to be sorted into three categories. Analysis of one of these categories shows how the subset has the molecular hallmarks and shortened survival of glioblastoma multiforme, the most lethal of brain tumors.
"The immediate clinical implication is that a group of patients with tumors previously categorized as lower grade should actually be treated as glioblastoma patients and receive that standard of care — temozolomide chemotherapy and irradiation," said Verhaak, Ph.D. lead author of the research.
"Classifying lower-grade tumors in these three molecular clusters more accurately characterizes them than current methods used to group and grade tumors," Verhaak said.
The pivotal molecular markers that define the three tumor clusters — mutational status of the IDH1 and IDH2 genes and loss of chromosome arms 1p and 19q — are already routinely checked in clinical care, Verhaak noted, so implementing the new categories can be done relatively quickly. MD Anderson News Release
Tumor-suppressor connects with histone protein to hinder gene expression
A team led by MD Anderson scientists also reported how a tumor-suppressing protein acts as a dimmer switch to dial down gene expression. It does this by reading a chemical message attached to another protein that’s tightly intertwined with DNA.
The findings, also published in the journal Nature on April 10, provide evidence in support of the "histone code" hypothesis. The theory holds that histone proteins, which combine with DNA to form chromosomes, are more intimately involved in gene expression than their general role of facilitating or hindering gene activation suggests.
The researchers found that high expression of the tumor-suppressor ZMYND11 is associated with longer survival for patients with triple-negative breast cancer.
"We also found that this variant, H3.3, is modified by methylation to create a specific epigenetic landscape that is accommodated by the tumor-suppressing protein ZMYND11. The protein in turn blocks gene activation," Shi said. "This is exactly the type of combined effect predicted by the histone code hypothesis."
Methylation, the attachment of a methyl group to a gene or protein, and other types of histone modifications are considered epigenetic factors, which modify a gene's behavior without changing its DNA coding.
Shi and colleagues found that the protein ZMYND11 "reads" the modified histone H3.3 by connecting to it where a tri-methyl chemical group binds to H3.3. From this position, Shi said, ZMYND11 thwarts a step in gene activation called elongation, inhibiting cancer growth.