Skip to main content

Genetic Study Identifies Myeloma

12-year genetic study identifies unique types of multiple myeloma


An unprecedented effort to sequence the genome, exome and RNA in tumors from patients with multiple myeloma defines distinct subtypes of the disease, according to an international team of scientists led by researchers from the Translational Genomics Research Institute (TGen), part of the City of Hope.

The findings of the 12-year observational study provide a clearer picture of the genetic changes that may be important in each subtype of this cancer of our antibody producing plasma cells, which is treatable but incurable. This information could help guide more personalized treatments in the future, the researchers write in Nature Genetics.

The scientists identified the genetic basis for a high-risk patient population, named "PR," that is associated with a median survival of under two years compared to the average survival in the study that exceeds eight years. About 25% of patients transitioned to the PR subtype during the study, and those who transitioned to PR had worse outcomes, with a median survival of 88 days after the transition.

"We've known about this subtype for over a decade and now replicated that this is a high-risk group of patients with the therapies used today. Clearly, these are patients who we need to get on clinical trials because the current drugs just don't work for them," said Jonathan Keats, Ph.D., assistant professor, director of Bioinformatics and Collaborative Sequencing Center at TGen, and a senior author on the paper.

"What we clearly showed is that there is a genetic basis for people being in the PR subgroup."

The study also "helps to highlight that late-stage disease is not like early-stage disease, and in an era where we're moving into early detection, drugs that work in the early stage may not be the drugs that work at the very late stage," Keats added.

The Multiple Myeloma Research Foundation (MMRF) Relating Clinical Outcomes in Multiple Myeloma to Personal Assessment of Genetic Profile (CoMMpass) study included 1,143 patients from 84 clinical sites located in the United States, Canada, Spain and Italy, enrolled between 2011 and 2015 and followed patients for at least eight years after diagnosis.

It is the largest single sequencing study of multiple myeloma patients to date, based on the number of patients and the number of sequencing assays performed.

"There's also clinical data on these patients collected every three months throughout their entire disease course, not just when they're genetically profiled, which is an absolute treasure trove," said Keats.

Two main groups of multiple myeloma patients have been known for some time: a hyperdiploid group with extra copies of chromosomes in tumor cells, and a non-hyperdiploid group with chromosomal rearrangements. The approach used by the current team of researchers helped them identify different subgroups within these broad categories.

"A lot of studies have looked at one method—they look at copy number state, or another one looks at if there are mutations—very few actually integrate the two to really understand how an individual gene is functioning in that patient," Keats noted. "For the field, we've provided a very robust list of candidate genes that are important in the disease."

Keats said the findings could change how doctors speak with their patients about crafting a treatment plan. Although the common belief is that hyperdiploid patients have more favorable overall survival, for instance, the researchers found that "hyperdiploid" encompasses five different groups of patients—one of which has significantly worse outcomes and could benefit from aggressive therapy.

One of the next challenges is to match medicines with specific genetic features, Keats said. "We've definitely answered the question of what different types there are, but not which drugs they best respond to."

TGen is building on this pioneering work to bring personalized medicine to multiple myeloma patients by launching clinical-grade whole genome sequencing in the TGen Clinical Lab. This test will provide patients and their care team with a complete picture of the genetics of each tumor along with prognostic information and therapeutic recommendations within 48 hours.

genetic study, myeloma, multiple myeloma, plasma cells, genetic mutations, blood cancer, therapeutic targets, genetic predisposition, chromosomal abnormalities, gene expression, personalized treatment, patient outcomes, genetic markers, myeloma progression, cancer research, targeted therapy, oncogenes, tumor suppressor genes, genomics, hematologic malignancies,

#GeneticStudy, #Myeloma, #MultipleMyeloma, #PlasmaCells, #GeneticMutations, #BloodCancer, #TherapeuticTargets, #GeneticPredisposition, #ChromosomalAbnormalities, #GeneExpression, #PersonalizedTreatment, #PatientOutcomes, #GeneticMarkers, #CancerResearch, #TargetedTherapy, #Oncogenes, #TumorSuppressorGenes, #Genomics, #HematologicMalignancies, #CancerGenetics

International Conference on Genetics and Genomics of Diseases 




For Enquiries: genetics@healthcarek.com 

Get Connected Here 
--------------------------------- 
--------------------------------- 
facebook.com/profile.php?id=61555903296992 
tumblr.com/blog/dorita0211 


Comments

Post a Comment

Popular posts from this blog

Chromosomal Abnormalities

  Chromosomal Abnormalities Chromosome abnormalities refer to structural or numerical changes in chromosomes that can disrupt normal genetic function, leading to developmental disorders, congenital abnormalities, and various genetic diseases. These abnormalities may arise from errors in cell division, such as nondisjunction or chromosomal breakage, resulting in conditions like Down syndrome , Turner syndrome, Klinefelter syndrome , and various deletion or duplication syndromes. Understanding chromosome abnormalities is essential for genetic counseling, prenatal diagnosis, disease risk assessment, and research in cytogenetics and molecular genetics. Chromosome abnormalities, chromosomal disorders, chromosomal mutations, aneuploidy, structural chromosome abnormalities, nondisjunction, deletion syndrome, duplication syndrome , translocation, inversion, cytogenetics, karyotyping, prenatal diagnosis , genetic testing, genomic instability, Down syndrome, Turner syndrome, Klinefelter syn...
Post a Comment
Read more

Human Brain Organoids

Human Brain Organoids Model Abnormal Prenatal Neural Development Induced by Thermal Stimulation The developing human foetal brain is sensitive to thermal stimulation during pregnancy. However, the mechanisms by which heat exposure affects human foetal brain development remain unclear, largely due to the lack of appropriate research models for studying thermal stimulation. To address this, we have developed a periodic heating model based on brain organoids derived from human pluripotent stem cells. The model recapitulated neurodevelopmental disruptions under prenatal heat exposure at the early stages, providing a paradigm for studying the altered neurodevelopment under environmental stimulation. Our study found that periodic heat exposure led to decreased size and impaired neural tube development in the brain organoids. Bulk RNA-seq analysis revealed that the abnormal WNT signalling pathway and the reduction of G2/M progenitor cells might be involved in heat stimulation. Further investi...
Post a Comment
Read more

Multifactorial Genetic Conditions

Multifactorial Genetic Conditions Multifactorial genetic conditions are disorders caused by the combined effects of multiple genes and environmental factors , rather than a single gene mutation . These conditions do not follow classic Mendelian inheritance patterns and instead result from complex gene–environment interactions . Factors such as lifestyle, nutrition, infections, stress, and exposure to toxins can significantly influence disease onset and severity in genetically susceptible individuals. Common examples include diabetes, cardiovascular diseases , neural tube defects, asthma, and many neuropsychiatric disorders. Understanding multifactorial inheritance is essential for risk prediction, preventive medicine, and personalized healthcare strategies. Multifactorial inheritance, polygenic traits, gene–environment interaction, complex diseases, genetic susceptibility, environmental risk factors, non-Mendelian inheritance, disease predisposition, polygenic risk score, precision ...
Post a Comment
Read more