Skip to main content

Susceptibility Genes Identified

Potential Sarcoma Susceptibility Genes Identified



Pathogenic variants were found in a substantial portion of 41 patients living with soft tissue sarcoma (STS), with experts highlighting 2 genes as playing vital roles in disease development: MYO5B and MYO3A.

Findings of the retrospective analysis were published in Acta Oncologica.

Pathogenic variants are considered risk factors for development of diseases/disorders. Their presence may not always result in an adverse outcome, but there is a greater likelihood of that occurring; particularly when these variants, also known as mutations, are inherited.

Among the overall patient population, the most common STS subtype was rhabdomyosarcoma (24 diagnoses), followed by synovial sarcomas (9 diagnoses), Ewing sarcoma (2 cases), and unclassified (6 cases). The patients ranged in age from 0 months to 22 years, comprising pediatric and young adult patient populations; their mean (median) age at diagnosis was 10.4 (11.0) years, and they received care between 1981 and 2019 at Haukeland University Hospital in Norway.

Seventeen percent of the 41 cases—22 female patients and 24 male patients overall, but only 41 patients had adequate tissue for sampling—exhibited pathogenic variants or likely pathogenic variants, the authors stated. The genes these were found in were TP53, MUTYH, FANCC, DICER1, FANCA, MYO3A, and MYO5B. For many sarcomas, the authors emphasized, there are a lack of data on how germline alterations contribute to these cancers in pediatric patients. They used both normal tissue samples and tumor tissue samples for their investigation, and analyzed the DNA from these samples through sequencing of a 360 cancer gene panel.

The most common tumor location was the extremities (28%), followed by the trunk (25%), head and neck area (22%), genitourinary tract (11%), pelvic or abdominal area (5.6% each), and gynecologic area (2.8%).

Of the genes identified, TP53, MUTYH, FANCC, DICER1, and FANCA are known cancer predisposition genes, while MYO3A and MYO5B have been linked to both cancer and deafness and microvillus inclusion disease, respectively, the authors noted.3,4 The authors also detected germline variants in MYO3A and MYO5B.

TP53, DICER1, FANCC, and FANCA have, in particular, been linked to a greater risk of rhabdomyosarcoma, with primary tumor types being embryonal rhabdomyosarcoma (TP53, DICER1), rhabdomyofibrosarcoma (FANCC), and osteosarcoma (FANCA). Patients, too, who had variants of MYO3A and MYO5B also had rhabdomyosarcoma.

“These genes have not previously been shown to be associated with elevated risk of either RMSs, Ewing sarcoma, or soft tissue sarcomas in general,” the authors wrote.

Overall, when drilling down to sarcoma subtypes, patients with rhabdomyosarcoma had 6 of these 7 identified variants while the patients diagnosed with synovial sarcoma or Ewing sarcoma had none. Results were similar when considering gender, with 4 of 7 and 3 of 7 found in the male patients and female patients, respectively.

Family history was also evaluated. Among the 3 patients who had a family history of cancer, these patients were shown in the present study to have variants in TP53, FANCA, and DICER.

Last, the study investigators examined variants of unknown significance, with the goal of findings previously unknown triggers of early-onset STS. With this analysis, they found 28 variants of unknown significance, and these included NOTCH2, ABL2, IDH1, EGFR, PAX9, and JAK3. The authors noted that few of these were recurring, with the entire patient population of their study harboring an average 0.7 variants of unknown significance, but that these variants affected “a broader repertoire”. There was an age gap in STS diagnosis between those with pathogenic variants (7 years) and variants of unknown significance (13 years), but this result was deemed not statistically significant.

“Although these observations should be seen as anecdotal observations,” the authors concluded, “we believe they warrant further investigations into the potential link between genetic alterations in developmental defect syndromes and sarcomas.”

brain function, cognition, memory, perception, attention, decision-making, neurons, synapses, neurotransmitters, neuroplasticity, brain structure, learning, brain health, mental stimulation, nutrition, exercise, sleep, Alzheimer's, stroke, traumatic brain injury, brain research,

#BrainFunction, #Cognition, #Memory, #Perception, #Attention, #DecisionMaking, #Neurons, #Synapses, #Neurotransmitters, #Neuroplasticity, #BrainStructure, #Learning, #BrainHealth, #MentalStimulation, #Nutrition, #Exercise, #Sleep, #Alzheimers, #Stroke, #BrainResearch

International Conference on Genetics and Genomics of Diseases

Visit: genetics-conferences.healthcarek.com

Award Nomination: x-i.me/gennom1
Award registration: x-i.me/genreg2
Member Nomination: x-i.me/genmember
Member Registration: x-i.me/genreg1
For Enquiries: genetics@healthcarek.com


Get Connected Here
---------------------------------
---------------------------------

Pinterest: x-i.me/genpt
Twitter: x-i.me/gentw
Facebook: x-i.me/genfb
Instagram: x-i.me/genin
Youtube: x-i.me/genyt

Comments

Popular posts from this blog

Fruitful innovation

Fruitful innovation: Transforming watermelon genetics with advanced base editors The development of new adenine base editors (ABE) and adenine-to-thymine/ guanine base editors (AKBE) is transforming watermelon genetic engineering. These innovative tools enable precise A:T-to-G and A:T-to-T base substitutions, allowing for targeted genetic modifications. The research highlights the efficiency of these editors in generating specific mutations, such as a flowerless phenotype in ClFT (Y84H) mutant plants. This advancement not only enhances the understanding of gene function but also significantly improves molecular breeding, paving the way for more efficient watermelon crop improvement. Traditional breeding methods for watermelon often face challenges in achieving desired genetic traits efficiently and accurately. While CRISPR/Cas9 has provided a powerful tool for genome editing, its precision and scope are sometimes limited. These limitations highlight the need for more advanced gene-e...

Genetic factors with clinical trial stoppage

Genetic factors associated with reasons for clinical trial stoppage Many drug discovery projects are started but few progress fully through clinical trials to approval. Previous work has shown that human genetics support for the therapeutic hypothesis increases the chance of trial progression. Here, we applied natural language processing to classify the free-text reasons for 28,561 clinical trials that stopped before their endpoints were met. We then evaluated these classes in light of the underlying evidence for the therapeutic hypothesis and target properties. We found that trials are more likely to stop because of a lack of efficacy in the absence of strong genetic evidence from human populations or genetically modified animal models. Furthermore, certain trials are more likely to stop for safety reasons if the drug target gene is highly constrained in human populations and if the gene is broadly expressed across tissues. These results support the growing use of human genetics to ...

Genetics study on COVID-19

Large genetic study on severe COVID-19 Bonn researchers confirm three other genes for increased risk in addition to the known TLR7 gene Whether or not a person becomes seriously ill with COVID-19 depends, among other things, on genetic factors. With this in mind, researchers from the University Hospital Bonn (UKB) and the University of Bonn, in cooperation with other research teams from Germany, the Netherlands, Spain and Italy, investigated a particularly large group of affected individuals. They confirmed the central and already known role of the TLR7 gene in severe courses of the disease in men, but were also able to find evidence for a contribution of the gene in women. In addition, they were able to show that genetic changes in three other genes of the innate immune system contribute to severe COVID-19. The results have now been published in the journal " Human Genetics and Genomics Advances ". Even though the number of severe cases following infection with the SARS-CoV-...