scholarly journals Investigation of an Alternative Marker for Hypermutability Evaluation in Different Tumors

Genes ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 197
Author(s):  
Anqi Chen ◽  
Suhua Zhang ◽  
Lei Xiong ◽  
Shihan Xi ◽  
Ruiyang Tao ◽  
...  
Keyword(s):  
Tandem Repeats ◽  
Cell Cancer ◽  
Objective Response ◽  
Hepatocellular Cancer ◽  
The Status ◽  
Promising Treatment ◽  
Gi Cancers ◽  
Tumor Types ◽  
Potential Threshold ◽  
Short Tandem

A growing number of studies have shown immunotherapy to be a promising treatment strategy for several types of cancer. Short tandem repeats (STRs) have been proven to be alternative markers for the evaluation of hypermutability in gastrointestinal (GI) cancers. However, the status of STRs and microsatellite instability (MSI) in other tumors have not yet been investigated. To further compare STR and MSI alterations in different tumors, a total of 407 paired DNAs were analyzed from the following eight tumor types: breast cancer (BC), hepatocellular cancer (HCC), pancreatic cancer (PC), colorectal cancer (CRC), gastric cancer (GC), lung cancer (LC), esophageal cancer (EC), and renal cell cancer (RCC). The STR alteration frequencies varied in different tumors as expected. Interestingly, none of the patients possessed MSI-low (MSI-L) or MSI-high (MSI-H), except for the GI patients. The highest STR alteration was detected in EC (77.78%), followed by CRC (69.77%), HCC (63.33%), GC (54.55%), LC (48.00%), RCC (40.91%), BC (36.11%), and PC (25.71%). The potential cutoff for hypermutability was predicted using the published objective response rate (ORR), and the cutoff of LC and HCC was the same as that of GI cancers (26.32%). The cutoffs of 31.58% and 10.53% should be selected for BC and RCC, respectively. In summary, we compared MSI and STR status in eight tumor types, and predicted the potential threshold for hypermutability of BC, HCC, CRC, GC, LC, EC, and RCC.

Population Genetics of Y-Chromosome Short Tandem Repeats in Humans

1997 ◽  
Vol 45 (3) ◽  
pp. 265-270 ◽  
Author(s):  
Anna Pérez-Lezaun ◽  
Francesc Calafell ◽  
Mark Seielstad ◽  
Eva Mateu ◽  
David Comas ◽  
...  
Keyword(s):  
Population Genetics ◽  
Y Chromosome ◽  
Short Tandem Repeats ◽  
Tandem Repeats ◽  
Short Tandem

Bayesian approach to discriminant problems for count data with application to multilocus short tandem repeat dataset

2020 ◽  
Vol 19 (2) ◽  
Author(s):  
Koji Tsukuda ◽  
Shuhei Mano ◽  
Toshimichi Yamamoto
Keyword(s):  
Sample Size ◽  
Classification Accuracy ◽  
Tandem Repeats ◽  
Bayes Factor ◽  
Characteristic Curve ◽  
Geometric Mean ◽  
Previous Method ◽  
Threshold Adjustment ◽  
Two Populations ◽  
Short Tandem

AbstractShort Tandem Repeats (STRs) are a type of DNA polymorphism. This study considers discriminant analysis to determine the population of test individuals using an STR database containing the lengths of STRs observed at more than one locus. The discriminant method based on the Bayes factor is discussed and an improved method is proposed. The main issues are to develop a method that is relatively robust to sample size imbalance, identify a procedure to select loci, and treat the parameter in the prior distribution. A previous study achieved a classification accuracy of 0.748 for the g-mean (geometric mean of classification accuracies for two populations) and 0.867 for the AUC (area under the receiver operating characteristic curve). We improve the maximum values for the g-mean to 0.830 and the AUC to 0.935. Computer simulations indicate that the previous method is susceptible to sample size imbalance, whereas the proposed method is more robust while achieving almost identical classification accuracy. Furthermore, the results confirm that threshold adjustment is an effective countermeasure to sample size imbalance.

Conditional Genotypic Probabilities for Microsatellite Loci

Genetics ◽  
2000 ◽  
Vol 155 (4) ◽  
pp. 1973-1980
Author(s):  
Jinko Graham ◽  
James Curran ◽  
B S Weir
Keyword(s):  
Short Tandem Repeats ◽  
Tandem Repeats ◽  
Dirichlet Distribution ◽  
Forensic Dna ◽  
Match Probability ◽  
Microsatellite Genotype ◽  
Allelic State ◽  
Forensic Assessments ◽  
Dna Profiles ◽  
Short Tandem

Abstract Modern forensic DNA profiles are constructed using microsatellites, short tandem repeats of 2–5 bases. In the absence of genetic data on a crime-specific subpopulation, one tool for evaluating profile evidence is the match probability. The match probability is the conditional probability that a random person would have the profile of interest given that the suspect has it and that these people are different members of the same subpopulation. One issue in evaluating the match probability is population differentiation, which can induce coancestry among subpopulation members. Forensic assessments that ignore coancestry typically overstate the strength of evidence against the suspect. Theory has been developed to account for coancestry; assumptions include a steady-state population and a mutation model in which the allelic state after a mutation event is independent of the prior state. Under these assumptions, the joint allelic probabilities within a subpopulation may be approximated by the moments of a Dirichlet distribution. We investigate the adequacy of this approximation for profiled loci that mutate according to a generalized stepwise model. Simulations suggest that the Dirichlet theory can still overstate the evidence against a suspect with a common microsatellite genotype. However, Dirichlet-based estimators were less biased than the product-rule estimator, which ignores coancestry.

403 Early results from a phase 1 study to evaluate safety, pharmacokinetics, and efficacy of AMG 404, a programmed death-1 (PD-1) antibody, in patients with advanced solid tumors

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A428-A428
Author(s):  
Timothy Price ◽  
Sant Chawla ◽  
Gerald Falchook ◽  
Hans Prenen ◽  
Iwona Lugowska ◽  
...  
Keyword(s):  
Partial Response ◽  
Solid Tumors ◽  
Clear Cell ◽  
Phase 1 ◽  
Cell Cancer ◽  
Objective Response ◽  
Study Endpoint ◽  
Primary Study ◽  
Pharmacokinetic Parameters ◽  
Advanced Solid Tumors

BackgroundEnhancement of antitumor immunity through inhibition of the checkpoint PD-1 receptor has been effective in the treatment of many malignancies. AMG 404 is a monoclonal antibody (mAb) targeting PD-1. This phase 1, open-label, multicenter first-in-human study (NCT03853109) will evaluate the safety, tolerability, pharmacokinetics, and efficacy of AMG 404 monotherapy in adult patients with advanced solid tumors.MethodsThe primary study endpoint is dose-limiting toxicity (DLT) and safety; key secondary endpoints include pharmacokinetic parameters, objective response rate (assessed Q8W), duration of response, and progression-free survival. Key inclusion criteria include histologically or cytologically proven metastatic or locally advanced solid tumors not amenable to curative treatment with surgery or radiation for which standard therapies have been exhausted or not available. Prior anti-PD-(L)1 or other checkpoint inhibitors were not allowed. Five dose-finding cohorts, including 2 expansion cohorts, ranged from 3–20 patients each. AMG 404 was given until disease progression, intolerance, or consent withdrawal.ResultsAs of the data cutoff date of May 4, 2020, 62 patients received at least 1 dose of AMG 404 and were included in the safety and efficacy analysis sets. Fifty percent were men, 72% had ECOG 1 performance status, median age was 62 years (range: 28–83), and 42% had ≥3 lines of prior anticancer therapy. Median AMG 404 exposure was ~3 months (maximum: ~12 months). No DLTs were observed. Treatment-related adverse events (TRAEs) were reported for 29 patients (47%): those reported for ≥2 patients were fatigue (n=7); hypothyroidism (n=6); increased blood thyroid stimulating hormone and nausea (n=4 each); increased aspartate aminotransferase, decreased appetite, and pyrexia (n=3 each); and increased alanine aminotransferase, arthralgia, diarrhea, and increased weight (n=2 each). AEs leading to withdrawal of AMG 404 were reported for 3 patients (5%); all were serious and considered to be not related to AMG 404. Sixteen (26%) patients died on study; no deaths were considered related to AMG 404. Preliminary pharmacokinetic results were consistent with those of other therapeutic anti-PD-1 mAbs. Three patients had a confirmed partial response (pancreatic cancer, clear cell cancer, and pleomorphic sarcoma); an additional 4 patients had one scan with a partial response and are pending a confirmatory scan (clear cell renal carcinoma, undifferentiated nasopharyngeal carcinoma, sarcomatoid carcinoma of unknown primary, and colon cancer).ConclusionsAMG 404 is tolerable at the tested doses with no DLTs reported. All observed TRAEs are consistent with other anti-PD-1 therapies. Encouraging anti-tumor activity has been observed in heavily pretreated patients. The study is continuing enrollment into additional cohorts.Trial RegistrationNCT03853109Ethics ApprovalThe study was approved by the Ethics Board of each institution involved in this study and can be produced upon request.

scholarly journals Short Tandem Repeats Define a Gestational Origin for Metastatic Choriocarcinoma

2019 ◽  
Vol 108 (2) ◽  
pp. e115-e117
Author(s):  
Kelly Brown ◽  
Robert Homer ◽  
Marina Baine ◽  
Justin D. Blasberg
Keyword(s):  
Short Tandem Repeats ◽  
Tandem Repeats ◽  
Short Tandem

scholarly journals Sex-Specific Migration Patterns in Central Asian Populations, Revealed by Analysis of Y-Chromosome Short Tandem Repeats and mtDNA

1999 ◽  
Vol 65 (1) ◽  
pp. 208-219 ◽  
Author(s):  
Anna Pérez-Lezaun ◽  
Francesc Calafell ◽  
David Comas ◽  
Eva Mateu ◽  
Elena Bosch ◽  
...  
Keyword(s):  
Y Chromosome ◽  
Short Tandem Repeats ◽  
Tandem Repeats ◽  
Migration Patterns ◽  
Asian Populations ◽  
Central Asian ◽  
Short Tandem
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