Hypertranscription in aggressive Tumors of 31 cancer types Is Linked to Poorer Cancer Outcomes

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"... A newly developed algorithm allowed researchers to measure transcription levels more accurately than ever before, leading to the discovery that the degree of hypertranscription in a patient’s tumor cells is fairly predictive of their survival chances ...
“This study finds that hypertranscription is pervasively co-opted by cancer cells across different types of cancer, and is correlated with poorer patient survival,” he says, adding that the work has several important implications, including raising awareness to the pervasiveness of hypertranscription in cancer and pointing to the phenomenon as a potential target for cancer therapies. ...
To get around this issue, the team developed a new computational tool, which they dubbed RNAmp. It uses the number of tumor-specific mutations as well as tumor-specific copy number changes—changes in chromosome structure that lead to gain or loss of DNA sections—to normalize RNA measures, allowing for accurate estimation of the transcription levels of tumor cells. ..."

From the abstract:

"Cancers are often defined by the dysregulation of specific transcriptional programs; however, the importance of global transcriptional changes is less understood. Hypertranscription is the genome-wide increase in RNA output. Hypertranscription’s prevalence, underlying drivers, and prognostic significance are undefined in primary human cancer. This is due, in part, to limitations of expression profiling methods, which assume equal RNA output between samples. Here, we developed a computational method to directly measure hypertranscription in 7494 human tumors, spanning 31 cancer types. Hypertranscription is ubiquitous across cancer, especially in aggressive disease. It defines patient subgroups with worse survival, even within well-established subtypes. Our data suggest that loss of transcriptional suppression underpins the hypertranscriptional phenotype. Single-cell analysis reveals hypertranscriptional clones, which dominate transcript production regardless of their size. Last, patients with hypertranscribed mutations have improved response to immune checkpoint therapy. Our results provide fundamental insights into gene dysregulation across human cancers and may prove useful in identifying patients who would benefit from novel therapies."

Hypertranscription by Tumors Is Linked to Poorer Cancer Outcomes: Study | The Scientist Magazine® The extent to which transcription is higher in tumor cells than in surrounding nontumor cells is associated with bad prognoses in several cancer types.

Widespread hypertranscription in aggressive human cancers (open access)

Fig. 1. Overview of RNA output analysis with RNAmp.