Scientists report new insights into the development of blood cancers

Utah researchers report important new perspectives on the development of blood cancers. In a work published today in Find blood cancer, a journal of the American Society for the Study of Cancer, scientists report a study of published data from more than 7,000 patients diagnosed with leukemia and other blood disorders. Their findings provide new evidence about mutations that can trigger cancer development and those that can help cancer to progress.

The researchers sought to identify dangerous areas of mutation, or frequent changes in specific areas of cancer patients ’genetic information. The researchers then used these hotspots to see if the same mutations were present in the DNA data of more than 4,500 people who were not diagnosed with cancer. They found that about 2 percent of these healthy participants, at low levels, had mutations similar to those commonly seen in cancer patients.

“It is a great benefit to understand how disease develops by studying people who are currently healthy but are on track to start a disease,” said Clint Mason, PhD, associate professor pediatrician at U of U, who specializes in cancer genomics and bioinformatics and led the study.

Variations occur across the 3 billion centers of DNA present in human cells. There is little effect on health, but some infections may cause or support the development of diseases, including cancer. So, scientists are working to find out which mutations have the biggest effects on health. In this study, the researchers attempted to understand what mutations are most commonly present in adults and children both with and without blood cancers. They hope that this information will clarify an understanding of these cancers, and in addition, they could be used to identify people who are progressing to cancer.

The team of researchers consisted almost entirely of Utah (U of U) University faculty and students. Mason was joined by co-authors Julie Feusier, PhD, a trainee in the human genetics department and now a postdoctoral fellow at the Huntsman Cancer Institute, and Sasi Arunachalam, PhD, a postgraduate at the Institute Huntsman Cancer and now a research associate at St Jude Children’s Research Hospital, in conducting analyzes with other co-authors.

For the first part of the study, the researchers completed a large-scale data mining study to examine published data from 48 cancer studies that reported mutations present in people experiencing it. leukemia or other hematologic malignancies. Across the 7,430 pediatric and adult cancer patients of these studies, 434 DNA locations were identified as frequently transfused. Then, in a subsequent study of many terabytes of publicly available genetic data, the researchers identified the same mutations associated with low-level cancer among 83 of the 4,538 people who, according to apparently, cancer-free.

When similar mutations are found in a small percentage of a healthy person’s blood cells, it may indicate that something extraordinary has started to happen. “

Clint Mason, PhD, Associate Professor of Pediatrics, U of U.

It has been previously discovered that this inflammatory process (known as clonal hematopoiesis) becomes more common as people age. As a result, researchers tend to focus on adult study when studying this phenomenon. But in this study, in addition to adults, the researchers analyzed data from 400 children who were likely to be cancer-free. They found preliminary evidence that early cancer mutations could be detected in this age group.

In accompanying statement, to be published by Find blood cancer in her section “In the Spotlight,” Barbara Spitzer, MD, and Ross Levine, MD, of the Sloan Cancer Kettering Cancer Memory Center, wrote, “This work shows the first evidence that [clonal hematopoiesis] observed in children outside those with progressive malignancies. “They also said,“ This expansion of the range of hotspot malignancy hematologic mutations goes beyond a better understanding of the molecular repertoire of hematologic malignancies… A more complete knowledge of relevant mutations could contribute to our detection of patients which has the greatest risk for malignant transformation. “

Finding a low-grade mutation equivalent to one that is frequently present at cancer studies could be frightening for a healthy person who is currently screened for such events. But fortunately, since cancer often requires multiple mutations to be present in a large fraction of cells, most people with low-grade mutation are less likely to develop cancer for several years or decades; if they develop cancer at all. Large lengthy studies are needed to identify the timeline in which specific mutations or a combination of mutations will accelerate progression to cancer.

The Utah researchers then hope to test the persistence of mutations identified at a younger age. This will provide an insight into their potential as biomarkers for those at greatest risk of cancer. Future intervention studies need to identify such.

“Our goal is to help fill gaps in understanding cancer development so that future prevention work can take place more quickly and effectively,” said Mason. “We are grateful that we have been able to has added a few puzzle pieces to that great effort. “