The Dana-Farber score predicts a multiple myeloma progress

A new risk assessment value developed by researchers from the Dana-Farber Cancer Institute and the Broad Institute of MIT and HARVARD shows how a multiple myeloma, a form of blood cancer, begins and develops by persecution of DNA mutations from precancator to malignant conditions. The evaluation, which is referred to as MM-like points, evaluates the severity of the disease and the risk of progression to active cancer, with higher values ​​indicating a faster progression. In the future, the MM-like score could be used in clinical practice to inform decisions about early interventions.

“In patients with a precursor state for a multiple myeloma, the multiple myeloma-like score helps, who has a higher risk of leading to active cancer,” says co-senior author Jean-Baptiste Alberge, PhD, trainer for medicine in Dana-Farber. “This study brings us closer to the personalized care of patients with a precursor stage of cancer and could better influence early intervention strategies in the future.”

The study was published in Nature Genetics.

Multiple myeloma is a cancer in plasma cells that affect 32,000 people in the United States every year. Before developing a multiple myeloma, the patients undergo the disease stages of the disease, which is called monoclonal gammopathy of indefinite significance (MGUS) or smoldering myeloma (SMM). About 1 to 10 percent of patients with these diseases lead to an active multiple myeloma per year, with 50 percent continued with high risk-SMM cases within two years.

“There was an urgent to identify genomic risk factors that predict the progression of the disease in the smoldering myeloma,” says Dr. Irene Ghobrial, director of the Center for Early Detection and Catching of Blood Cancer in Dana-Farber. “This applies in particular if we start with an early therapeutic intercept for SMM with high risk. Our data offer a simple genomic score that can help predict progress and improve our clinical markers to speed up the risk for our patients.”

Existing riskratification models for multiple myeloma characterize patients as “high” or “low” risk based on tumor stress measures. These models do not contain any genetic factors. The MM-like value defined in this study focuses on the presence and the progressive development of genetic anomalies to assess the state of the disease. The MM-like score increases over time with the accumulation of mutations that drive the disease.

“The risk as simply 'high' or 'low' treats the complexity of the tumor and development, and we have seen the opportunity to redefine it by sequencing the entire genome,” says Alberge.

Together with the Co-First authors Ankit Dutta, PhD, a postdoctoral in the GHobrial Laboratory, Andrea Poletti, PhD, a postdoctoral at the University of Bologna, Italy and collaborators from Great Britain, Germany and Greence, Alberge, Alberge, the mostly set people with merchants with multiple and multiple and Multiple with multiple and over 1000 people with multiple-myeloma and regulations. Smm. The study provides one of the largest analyzes of total genome data for the previous myeloma and its precursor conditions.

“This study significantly improves our ability to discover both potentially clinical-effective cancer mutations in MM, and the time when these events occur in illness states,” says GAD Getz, PhD director for Cancer Genome Computational Analysis at Broad Institute of MIT and HARVARD and BIOININFORTATIK in the Cancer Center for Cancer Research and Department for Pathology at the Massachusetts. “These findings would not be possible without access to deep sequences of whole genomes from a large number of patients and across various disease stages.”

By comparing mutations that were found more often in active illnesses than in asymptomatic precursor forms, they were able to identify genes that are probably associated with transformation to active diseases. The study also resulted in the likely order and the time of genetic mutations.

In order to validate the score, the team evaluated 47 tumor rehearsals from 20 patients at various points in the progress of the disease. They found that the MM-like values ​​in individual patients reflected the course of their illness in several cases. For example, 11 out of 13 patients who did not make progress during the observation period had a stable MM-like values, and 5 out of 7 patients who made progress, had MM scores that increased at the time of the progression.

The study also revealed surprising results about the origins of the multiple myeloma. In this study, the team estimates that the earliest genomic changes in connection with the illness in the patient's 20s or 30s can appear very early, although the multiple myeloma is usually diagnosed much later.

In order to make the MM-like score more clinically accessible, the team develops a test that is based on liquid biopsies instead of bone marrow biopsies to collect DNA. This change may make more frequent monitoring of the development of the condition. In addition, the team wants to continue to validate and improve the score by examining more patients over longer periods.

Financing: Multiple Myeloma Research Foundation, Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, International Myeloma Society, Dana-Farber Cancer Institute, Krouse Family Foundation, the National Institutes of Health and are cancer.