Using a new method of technology and computing, researchers at the Fred Hutch Cancer Center and the MD Anderson Cancer Center breasts.
In the study, published in ScienceThe researchers discovered that the amount of a specific enzyme, RNA polymerase II (RNAPII), which is found in histone genes, was associated with aggressiveness and tumor recurrence. Rnapii hyperelevant levels in these histone genes indicate the overcrehens of cancer and potentially contribute to chromosomal changes. These findings point to the use of a new genomic technology as a possible diagnostic and prognosis tool of cancer, which could improve precision oncology approaches.
“It has been overlooked that histone genes could be a limiting speed factor in cell replication and, in turn, a strong indicator of the proliferation of tumor cells,” said Ye Zheng, Ph.D., co -Suthor and assistant professor of bioinformatics and computational biology in MD Anderson. “This is because the current RNA sequencing methods cannot detect Histonas RNA due to their unique structure, which means that these libraries have greatly underestimated their presence. Our novel approach, combining a new experimental technology and a computational pipe , establishes a comprehensive ecosystem that can take advantage of multiple types of cancer to improve the diagnosis and prognosis of the tumor. “
The new technology produces better quality sampling data for decades
The results of the study were possible thanks to a new profile technology developed in the Steven Henikoff laboratory, Ph.D., co-director author and teacher in the Basic Sciences Division of Fred Hutch, which allows researchers to better study the best gene expression using formalin samples set with paraffin (FFPE).
Tissue biopsies are commonly stored for long -term use such as FFPE samples, but sample RNA becomes increasing quality.
The new technology, low chromatin neckline directed (Cutc), focuses on small fragmented DNA sequences that are not encoded in the DNA where Rnapii joins, located on the same chromosome as the gene they regulate, which allows scientists Direct directly the activity of the gene transcription of the gene transcription of the transcription of the transcription. DNA
When examining clinical samples using Cutc technology in various types of cancer, researchers found that histone gene expression was consistently and significantly greater in tumor samples compared to normal tissue samples.
Histona proteins provide an essential structural support for DNA on chromosomes, which act as reels around which DNA is wrapped. These proteins have been well studied, but most of the current tools to study gene expression are based on RNA sequencing. Histonas RNA is unique in the sense that its structure prevents RNA molecules from being detected by current methods.
Therefore, histone gene expression can be significantly underestimated in tumor samples. The researchers raised the hypothesis that the greatest proliferation of cancer cells leads to a very high expression, or hypertranscription, of histones to meet the additional demands of replication and cell division.
Rnapii’s expression correlates and predicts the aggressiveness of cancer
To prove their hypothesis, the researchers used the cuttac profile to examine and map RNAPII, which transcribes the DNA to the precursors of the messenger RNA. They studied 36 FFPE samples of patients with meningioma, a common and benign brain tumor, and used a new computational approach to integrate these data with almost 1,300 publicly available clinical data samples and corresponding clinical results.
In tumor samples, Rnapii enzyme signals found in histone genes could reliably distinguish between cancer and normal samples.
Rnapii signals in histone genes also correlated with clinical degrees in meningiomas, precisely predicting rapid recurrence, as well as the tendency of losses of full arm chromosomes. The use of this technology in FFPE samples of breast tumor of 13 patients with invasive breast cancer also predicted the aggressiveness of cancer.
“The technique we develop to examine the samples of preserved tumors now reveals a previously overlooked mechanism of cancer aggressiveness,” said Henikoff, who is also a researcher at the Howard Hughes medical institute. “Identifying this mechanism suggests that it could be a new test to diagnose cancers and possibly treat them.”
Zheng and his colleagues plan to use this technology in multiple types of cancer FFPE for greater validation.
This research was supported by the Howard Hughes Medical Institute, the National Health Institutes (HG012797) and the National Cancer Institute (T32CA009515). Here you can find a complete list of collaborating authors and their disseminations.
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