Latest news with #TP53
Medscape
10 hours ago
- Health
- Medscape
Fast Five Quiz: Cancer Diagnostics and Precision Medicine
Over the past decade, precision medicine has transformed cancer diagnostics and treatment by tailoring therapy to a patient's tumor biology based on molecular alterations rather than histologic subtypes or origins. Precision oncology often relies on molecular profiling through next-generation sequencing (NGS) to identify genomic events that can guide management. Techniques like targeted panels, whole-exome sequencing (WES), and whole-genome sequencing (WGS) provide different analysis levels, chosen based on tumor type, tissue, and therapy relevance. How much do you know about cancer diagnostics and precision medicine? Test your knowledge with this quick quiz. WGS is an NGS method that analyzes the entire DNA sequence of an organism, including both coding and noncoding regions. WGS offers broad genomic coverage, detecting structural variants, intergenic mutations, and copy number changes often missed by targeted methods. Clinically, it has been useful in identifying ERBB2 ( HER2 ) amplifications in breast cancer or complex epidermal growth factor receptor ( EGFR ) alterations in lung cancer that might not be captured by smaller panels, helping guide targeted therapy. However, its lower sequencing depth (30-60×) typically limits the detection of low-frequency variants in heterogeneous tumors, such as a subclonal TP53 mutation affecting a small subset of cells and potentially impacting treatment response, which WGS may miss due to its lower depth. WES focuses only on the protein-coding regions, offering greater depth than WGS but limited breadth; however, it misses important regulatory and noncoding mutations. For example, TERT promoter mutations in glioblastoma are clinically relevant but lie outside the exome and would be missed by WES. Targeted panels are NGS tests that focus on specific disease-related genes and, until recently, were the predominant method used for comprehensive genomic profiling in clinical settings. They offer high depth for detecting low-frequency, actionable mutations but have limited coverage and might miss rare alterations outside the selected genes. Sanger sequencing is a method that reads DNA by generating fragments of varying lengths using chain-terminating nucleotides. It is accurate for small regions but has low throughput and cannot detect low-frequency mutations, making it unsuitable for large-scale cancer genomics. Unlike WGS, which surveys the entire genome, Sanger covers only targeted regions, so it does not offer broad genomic coverage and is therefore not the correct answer. Learn more about molecular profiling in oncology diagnostics. TS panels analyze specific genes relevant to oncology, and by focusing on a smaller subset of the genome (a few dozen to a few hundred genes), these panels require fewer sequencing data, resulting in faster turnaround times and simplified data interpretation compared with WGS or WES. This targeted approach enhances sensitivity for detecting clinically actionable somatic mutations, especially in small or heterogeneous tumor samples. For example, targeted NGS panels in non-small cell lung cancer (NSCLC) can rapidly detect EGFR mutations, ALK rearrangements, and other actionable alterations, allowing oncologists to initiate targeted therapies based on the mutation profile promptly. TS also demands less data storage and computational processing compared with WGS or WES, resulting in faster turnaround times and lower costs. These attributes make TS especially well-suited for clinical settings where accuracy, speed, and cost-effectiveness are paramount Learn more about clinical practice guidelines in the use of precision medicine in oncology. Tissue is generally preferred for initial genomic profiling because it contains a higher concentration of tumor DNA, allowing for more accurate detection of somatic mutations. This is especially important in early-stage cancers or tumors that do not shed much DNA into the bloodstream to be detectable by liquid biopsy. The tissue also allows for additional analyses like immunohistochemistry for PD-L1 or assessment of tumor histology to guide therapy. Further, immunohistochemistry plays an important role in precision medicine by identifying protein biomarkers to help determine the use of immune checkpoint inhibitors in NSCLC, triple-negative breast cancer, and urothelial carcinoma. Blood-based tests (ie, liquid biopsies) generally yield lower tumor DNA and do not inherently offer deeper sequencing but are generally more cost-effective than tissue biopsies. Regulatory agencies currently accept blood-based tests (eg, FDA-approved liquid biopsies), but they are typically used when tissue is unavailable or there is insufficient tissue. Learn more about tissue-based profiling Liquid biopsy, particularly through the analysis of circulating tumor DNA (ctDNA), has emerged as a valuable tool for monitoring MRD after treatment. By detecting small amounts of tumor-derived genetic material in the blood, liquid biopsy enables early identification of molecular relapse, often before clinical or radiographic evidence of recurrence is apparent. This makes it particularly useful in post-treatment surveillance of cancers such as colorectal, breast, and NSCLC. Diagnosing lymphomas typically requires tissue biopsy to assess architectural patterns and immunophenotyping; it is also commonly regarded as the standard for diagnosis. PD-L1 expression is a protein-based biomarker typically measured by immunohistochemistry on tissue samples, not usually through ctDNA. However, researchers have stated, 'ctDNA response is a potential biomarker for predicting the efficacy and prognosis of first-line PD-1 inhibitor therapy combined with chemotherapy' in patients with advanced gastric cancer. ctDNA also has been shown to predict responses in patients using PD-1/PD-L1 immune checkpoint inhibitors. Tumor staging usually relies on imaging modalities and pathologic evaluation rather than ctDNA analysis alone. Learn more about clinical practice guidelines in the use of precision medicine in oncology. A high TMB is considered useful because it is associated with abnormal proteins that make the tumor more recognizable to the immune system. TMB is measured using NGS by counting the number of somatic, nonsynonymous mutations per megabase of DNA; it is typically assessed using WES or large targeted panels. A TMB of 10 or more mutations per megabase is considered 'high,' based on data from the KEYNOTE-158 trial. This led to the FDA approval of an immune checkpoint inhibitor for TMB-high solid tumors, for example. High TMB is not usually linked to fewer side effects; side effect profiles tend to depend on the therapy, not mutation count. Low TMB has been shown to lead to fewer neoantigens and typically less immune visibility. Typically, TMB directly measures the number of mutations, not PD-L1 protein expression. Learn more about immunotherapy diagnostics.
Yahoo
5 days ago
- Health
- Yahoo
This gene stops elephants from getting cancer – can it help human cancer research?
If you purchase an independently reviewed product or service through a link on our website, BGR may receive an affiliate commission. For decades, scientists have puzzled over a curious phenomenon called Peto's Paradox. In theory, large animals with long lifespans should develop cancer more often because they have more cells and more time for mutations to occur. Yet elephants, whales, and other giants of the animal world tend to get cancer far less often than humans do. Now, researchers are learning why. In a 2015 study, scientists discovered that elephants carry 19 extra copies of a powerful cancer-stopping gene called TP53. This gene acts as a genetic safeguard, detecting DNA damage and triggering cell death in potentially cancerous cells. For elephants, this enhanced genetic armor likely explains why they enjoy such low rates of cancer despite their size. Today's Top Deals Best deals: Tech, laptops, TVs, and more sales Best Ring Video Doorbell deals Memorial Day security camera deals: Reolink's unbeatable sale has prices from $29.98 However, a new study has broadened this investigation to nearly 300 animal species. The researchers analyzed over 16,000 necropsy records and found that elephants are not alone. Many other species have evolved their own cancer resistance strategies. Some birds, bats, and even lizards showed remarkably low levels of cancer, while animals like ferrets and opossums had much higher rates. The study also shed light on how various traits influence cancer risk, and it isn't always related to how many copies of the cancer-stopping gene an animal has. Larger body mass was linked to a slightly higher chance of developing cancer, though not as strongly as expected. Longer gestation periods appeared to lower cancer risk, possibly because of enhanced cellular safeguards developed during extended fetal growth. However, the researchers found that animals in captivity did not show artificially high cancer rates due to living longer than they would in the wild. But what does this mean for human cancer research? Well, TP53 is already a key player in human cancer prevention and assessing cancer risks, but humans only have two copies of the gene. Learning how elephants and other species enhance their cancer defenses could lead to new cancer treatments that make human cells more resilient. The hope researchers have is that mimicking or boosting the effects of this cancer-stopping gene could help doctors develop therapies to reduce cancer incidence or slow its progression. Comparative oncology, the field that studies cancer across different species, is only just beginning to unlock these secrets. The next steps will involve exploring how other animals resist cancer and finding ways to translate those discoveries into medical advances for humans. More Top Deals Amazon gift card deals, offers & coupons 2025: Get $2,000+ free See the
Medscape
10-06-2025
- Health
- Medscape
Fast Five Quiz: Low-Risk Myelodysplastic Syndrome
Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal hematopoietic stem cell disorders, each with varying levels of prognosis. Risk stratification is an important component of MDS; however, even lower-risk variants require a nuanced approach to management, and certain factors can further affect patient risk after diagnosis. What do you know about low-risk MDS? Check your knowledge with this quick quiz. Among the gene mutations identified that can influence the prognosis in MDS, SF3B1 mutation is strongly associated with favorable clinical outcomes. Other mutations such as such as TP53 , ASXL1 , EZH2 , ETV6 , and RUNX1 typically lead to poorer clinical outcomes. The National Comprehensive Care Network (NCCN) notes that combining analysis of these mutations in MDS with International Prognostic Scoring System (IPSS) can improve risk stratification beyond the strengths of the IPSS alone, which is standard practice in some treatment centers. Learn more about cytogenic studies for MDS. Data have shown that hypocellular bone marrow is one of several factors that predict good response to IST in patients with lower-risk MDS. The NCCN specifically recommends IST in select patients, generally those 'aged ≤60 years and with ≤5% marrow blasts, or those with hypocellular marrows, PNH clone positivity, or STAT-3 mutant cytotoxic T-cell clones.' Other factors associated with predicted benefit from IST include presence of dysplasia, young age (< 60 years), presence of HLA DR15, female sex, absence of ring sideroblasts, presence of trisomy 8, and relatively short duration of transfusion need. Learn more about hypocellular marrow in MDS. A study of patients with very low- and low-risk MDS found that mutations in three genes, IDH1 , IDH2 , and NPM1 , are more common among those patients with direct transformation to AML. NPM1 mutations are the most frequently-seen mutation in AML and are found in approximately 30%-35% of cases among adults. Mutations in ASXL1 , CBL , and TP53 were found to be associated with progression to higher-risk MDS but not with transformation to AML. Learn more about cytogenetics in MDS. According to a review published in JAMA , the median survival time for patients with low and very low risk MDS is 5.3 years and 8.8 years, respectively. This is consistent with other recent data. Collected data from the same JAMA review indicated that the median age for MDS diagnosis is approximately 70 years and is more common in males; chemotherapy and radiation therapy exposure are also reported significant risk factors. Further, the IPSS, revised-IPSS, and WHO classification-based prognostic scoring system are the most frequently used scoring systems for MDS risk. Learn more about MDS risk staging. Due to longer survival, patients with low-risk MDS might be given multiple red blood cell transfusions as part of their management (which could potentially lead to iron overload). To decrease iron overload, the NCCN recommends consideration of daily iron chelation with subcutaneous deferoxamine or oral deferasirox after > 20-30 transfusions. This approach is especially recommended for patients with lower-risk MDS or those who are potential candidates for transplantation. Learn more about iron chelation in MDS. Editor's Note: This article was created using several editorial tools, including generative AI models, as part of the process. Human review and editing of this content were performed prior to publication.
Yahoo
31-05-2025
- Health
- Yahoo
Sperm donor's genetic mutation linked to cancer in 10 conceived children
Sperm from a single donor in Europe has reportedly been used to conceive at least 67 pregnancies, although the donor carried a rare cancer-causing mutation. The donor's mutation has been linked to cancer diagnoses in 10 of these children, according to a report by The Guardian. The case was brought to light after two families separately contacted their fertility clinics after their children's cancer diagnoses were linked to a rare genetic variant called TP53. Prostate Cancer Risk Increases By 45% Among Men Who Share One Troubling Behavior A mutation in the TP53 gene causes Li-Fraumeni syndrome, which increases the risk of developing cancer. Cleveland Clinic states that this disorder comes with a 90% chance of developing some type of cancer by age 60, and a 50% chance by the age of 40. The European Sperm Bank, the sperm supplier, confirmed that this variant was present in some of the donor's sperm. Read On The Fox News App The Guardian reported that the rare variant was "not known to be linked to cancer at the time of donation in 2008." The genetic variant reportedly would not have been detectable through standard screening, and the donor is said to currently be in good health. Dr Edwige Kasper, a biologist at Rouen University Hospital in France, presented this case at the European Society of Human Genetics' annual conference in Milan last week, commenting on the need for a European limit on the number of births or families for a single donor. "We can't do whole-genome sequencing for all sperm donors – I'm not arguing for that," she told The Guardian. "But this is the abnormal dissemination of genetic disease. Not every man has 75 children across Europe." 4 Troubling Cancer Trends You Must Know About In 2025 Kasper analyzed the mutation in her lab, concluding that it was most likely cancer-causing and that children born from this donor should "receive genetic counseling." The research-turned-investigation tracked down 67 children from 46 families in eight European countries. The children were tested, with the variant detected in 23 of them. The 10 who had been diagnosed with cancer reportedly included cases of leukemia and non-Hodgkin lymphoma. In a statement sent to Fox News Digital, the European Sperm Bank stated that donor-assisted reproduction "generally remains a significantly safer alternative" than reproduction without genetic screening. The bank added that sperm donors undergo a "comprehensive health screening," which includes an in-depth medical examination, a review of the donor's family medical history and "extensive" testing for genetic and infectious diseases. "However, it's not possible to rule out all risks — and, in this particular case, the identified mutation is one that could not have been detected by the screening methods we use in accordance with regulations and would require specialized genetic testing," the group noted. Julie Paulli Budtz, VP. of corporate communications at the European Sperm Bank, expressed to Fox News Digital that they are "deeply affected by this case." Click Here To Sign Up For Our Health Newsletter "The donor has been thoroughly tested even beyond the required standards, but preventative genetic screening is reaching its limits here," she said. "Every human being has about 20,000 genes, and it is scientifically simply not possible to detect disease-causing mutations in a person's gene pool if you don't know what you are looking for." Budtz noted that the European Sperm Bank welcomes "continued dialogue" regarding setting an "internationally binding family limit," which they have advocated for "on several occasions, also at EU level." "This is also why, in addition to complying with national pregnancy limits, we have proactively implemented our own international limit of 75 families per donor," she added. In the U.S., there is no official legal limit on how many sperm donations one man can make. However, the American Society for Reproductive Medicine (ASRM) recommends that donors are limited to 25 live births within each population area of 800,000 people. "Institutions, clinics and sperm banks should maintain sufficient records to allow a limit to be set for the number of pregnancies for which a given donor is responsible," the ASRM states on its website. California Cryobank, which has claimed to have the largest selection of sperm and egg donations in the country, states on its website that it closely monitors donors to limit the total number of family units to 20 to 30 worldwide. "Limiting donor vials is an important part of the process," the bank noted. The U.S. Federal Drug Administration (FDA) requires that all sperm donors undergo a physical exam, complete a questionnaire, provide their medical history, and undergo screenings for infectious diseases at an FDA-approved lab. In addition, the ASRM suggests that donors undergo psychological and genetic screening, and also recommends infectious-disease testing of the recipient and the recipient's sexually intimate partners, per its website. For more Health articles, visit "Legal consultation and laws may vary by state," the organization notes. At California Cryobank, donors must be tested for infectious diseases, undergo genetic screening, get a psychological assessment and criminal background check, and receive screening for the Zika virus, according to the bank's article source: Sperm donor's genetic mutation linked to cancer in 10 conceived children
Fox News
31-05-2025
- Health
- Fox News
Sperm donor's genetic mutation linked to cancer in 10 conceived children
Sperm from a single donor in Europe has reportedly been used to conceive at least 67 pregnancies, although the donor carried a rare cancer-causing mutation. The donor's mutation has been linked to cancer diagnoses in 10 of these children, according to a report by The Guardian. The case was brought to light after two families separately contacted their fertility clinics after their children's cancer diagnoses were linked to a rare genetic variant called TP53. A mutation in the TP53 gene causes Li-Fraumeni syndrome, which increases the risk of developing cancer. Cleveland Clinic states that this disorder comes with a 90% chance of developing some type of cancer by age 60, and a 50% chance by the age of 40. The European Sperm Bank, the sperm supplier, confirmed that this variant was present in some of the donor's sperm. The Guardian reported that the rare variant was "not known to be linked to cancer at the time of donation in 2008." The genetic variant reportedly would not have been detectable through standard screening, and the donor is said to currently be in good health. "The identified mutation is one that could not have been detected by the screening methods we use in accordance with regulations." Dr Edwige Kasper, a biologist at Rouen University Hospital in France, presented this case at the European Society of Human Genetics' annual conference in Milan last week, commenting on the need for a European limit on the number of births or families for a single donor. "We can't do whole-genome sequencing for all sperm donors – I'm not arguing for that," she told The Guardian. "But this is the abnormal dissemination of genetic disease. Not every man has 75 children across Europe." Kasper analyzed the mutation in her lab, concluding that it was most likely cancer-causing and that children born from this donor should "receive genetic counseling." The research-turned-investigation tracked down 67 children from 46 families in eight European countries. The children were tested, with the variant detected in 23 of them. The 10 who had been diagnosed with cancer reportedly included cases of leukemia and non-Hodgkin lymphoma. In a statement sent to Fox News Digital, the European Sperm Bank stated that donor-assisted reproduction "generally remains a significantly safer alternative" than reproduction without genetic screening. The bank added that sperm donors undergo a "comprehensive health screening," which includes an in-depth medical examination, a review of the donor's family medical history and "extensive" testing for genetic and infectious diseases. "However, it's not possible to rule out all risks — and, in this particular case, the identified mutation is one that could not have been detected by the screening methods we use in accordance with regulations and would require specialized genetic testing," the group noted. Julie Paulli Budtz, VP. of corporate communications at the European Sperm Bank, expressed to Fox News Digital that they are "deeply affected by this case." "The donor has been thoroughly tested even beyond the required standards, but preventative genetic screening is reaching its limits here," she said. "Every human being has about 20,000 genes, and it is scientifically simply not possible to detect disease-causing mutations in a person's gene pool if you don't know what you are looking for." Budtz noted that the European Sperm Bank welcomes "continued dialogue" regarding setting an "internationally binding family limit," which they have advocated for "on several occasions, also at EU level." "This is also why, in addition to complying with national pregnancy limits, we have proactively implemented our own international limit of 75 families per donor," she added. In the U.S., there is no official legal limit on how many sperm donations one man can make. However, the American Society for Reproductive Medicine (ASRM) recommends that donors are limited to 25 live births within each population area of 800,000 people. "Institutions, clinics and sperm banks should maintain sufficient records to allow a limit to be set for the number of pregnancies for which a given donor is responsible," the ASRM states on its website. "Limiting donor vials is an important part of the process." California Cryobank, which has claimed to have the largest selection of sperm and egg donations in the country, states on its website that it closely monitors donors to limit the total number of family units to 20 to 30 worldwide. "Limiting donor vials is an important part of the process," the bank noted. The U.S. Federal Drug Administration (FDA) requires that all sperm donors undergo a physical exam, complete a questionnaire, provide their medical history, and undergo screenings for infectious diseases at an FDA-approved lab. In addition, the ASRM suggests that donors undergo psychological and genetic screening, and also recommends infectious-disease testing of the recipient and the recipient's sexually intimate partners, per its website. For more Health articles, visit "Legal consultation and laws may vary by state," the organization notes. At California Cryobank, donors must be tested for infectious diseases, undergo genetic screening, get a psychological assessment and criminal background check, and receive screening for the Zika virus, according to the bank's website.
