Detecting genetic hypermutability of gastrointestinal tumor by using a forensic STR kit

Chen, Anqi; Zhang, Suhua; Li, Jixi; Ji, Chaoneng; Chen, Jinzhong; Li, Chengtao

doi:10.1007/s11684-019-0698-4

Cited by 7 publications

(14 citation statements)

References 34 publications

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“…Three types of STR alterations were defined, as previously reported [9]. In the present study, a total of 1016 STR alterations were observed in the 407 paired tumor samples.…”

Section: Loss Of Heterozygosity Was the Most Commonly Observed Alteration In Eight Types Of Tumormentioning

confidence: 59%

“…The structure of MSI and STRs are both repeated nucleotides unit, and thus they may share the same heredity origin and may be useful for hypermutability evaluation. In our previous study, using a forensic STR kit, we found that more alterations could be detected in STRs compared to conventional MSI detection, which indicated more potential immunotherapy beneficiaries in CRC and GC [9]. However, the tumor types were limited to only GI tumors, and the alteration status in other major types of cancers remained unknown.…”

Section: Discussionmentioning

confidence: 99%

“…STR status was classified with the paired samples by investigating for the detection of genotypes among the 19 somatic STR markers (CSF1PO, D12S391, D13S317, D16S539, D18S51, D19S433, D21S11, D2S1338, D3S1358, D5S818, D6S1043, D7S820, D8S1179, FGA, Penta D, Penta E, TH01, TPOX, and vWA). Against the control STR type, three types of STR alterations were determined and calculated for the respective samples, as previously mentioned [9], namely allelic loss (L), occurrence of an additional allele (Aadd), and occurrence of a new allele (Anew). Briefly, L was defined when the peak ratio in the tumor sample/corresponding peak ratio in control blood was <0.5 or >2.…”

Section: Evaluation Of Microsatellite Instablity Stability and Short Tandem Repeats Alteration Statusmentioning

confidence: 99%

“…Previously, we generated a method, using short tandem repeat (STR) markers, for screening patients who might possess hypermutability. However, the sample types were limited to colorectal cancer (CRC) and gastric cancer (GC) only [9], and further studies on STR status in other type of tumors are needed. Worldwide, MSI status evaluation has been routinely tested in CRC and is now considered a generalized cancer phenotype [10,11].…”

Section: Introductionmentioning

confidence: 99%

“…Many studies have been carried out for MSI evaluation in both colorectal [12] and noncolorectal cancer [13], which have included NGS-based large-scale analysis, PCR-based microsatellite detection, and screening for loss of MMR protein expression using immunohistochemistry [10]. In our previous study [9], we investigated the MSI status of GI using six microsatellite markers, but performance in other tumor samples remains unknown. Therefore, evaluating MSI status in other tumor types is also important.…”

Section: Introductionmentioning

confidence: 99%

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Investigation of an Alternative Marker for Hypermutability Evaluation in Different Tumors

Chen

Zhang

Xiong

et al. 2021

Genes

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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.

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“…Three types of STR alterations were defined, as previously reported [9]. In the present study, a total of 1016 STR alterations were observed in the 407 paired tumor samples.…”

Section: Loss Of Heterozygosity Was the Most Commonly Observed Alteration In Eight Types Of Tumormentioning

confidence: 59%

Section: Discussionmentioning

confidence: 99%

Section: Evaluation Of Microsatellite Instablity Stability and Short Tandem Repeats Alteration Statusmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Investigation of an Alternative Marker for Hypermutability Evaluation in Different Tumors

Chen

Zhang

Xiong

et al. 2021

Genes

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show abstract

Solution to a case involving the interpretation of trace degraded DNA mixtures

Chen,

Tao

et al. 2024

Int J Legal Med

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Investigation on the Genetic-Inconsistent Paternity Cases Using the MiSeq FGx System

Chen

Tao

et al. 2022

Forensic Sciences Research

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Mutations might challenge the paternity index calculation in forensic identification. While many studies have focussed on the autosomal short tandem repeats (A-STR), the mutation status of sex chromosomes and single nucleotide polymorphism (SNP) remain blank. Next generation sequencing (NGS), known as high throughput and large sequence polymorphism, is a promising tool for forensic genetics. To describe the mutation landscapes in the paternity cases with genetic inconsistencies, a total of 63 parentage confirmed paternity cases contained at least one mismatched locus have been collected. The mutations were subsequently evaluated using Verogen’s MPS ForenSeq TM DNA Signature Kit and a microsatellite instability (MSI) detection kit. The result showed 98.41% (62/63) of the cases had no additional autosomal mutations even when the number of A-STRs increased to 27. As for the sex chromosomes, about 11.11% (7/63) of the cases exhibited either X-STR or Y-STR mutations. D2S1338, FGA and Penta E were the most frequent altered STRs, which suggested they might be the mutation hotspots. In addition, a male with sex chromosome abnormality was observed accidently, whose genotype might be 47, XXY, rather than MSI. Nearly 56.90% of the STR loci possessed isoalleles, which might result in higher STR polymorphisms. No Mendelian incompatibility was detected among the SNP markers, which indicated that SNP was a more reliable genetic marker in the genetic-inconsistent paternity cases. Supplemental data for this article is available online at https://doi.org/10.1080/20961790.2021.2009631 .

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Detecting genetic hypermutability of gastrointestinal tumor by using a forensic STR kit

Cited by 7 publications

References 34 publications

Investigation of an Alternative Marker for Hypermutability Evaluation in Different Tumors

Investigation of an Alternative Marker for Hypermutability Evaluation in Different Tumors

Solution to a case involving the interpretation of trace degraded DNA mixtures

Investigation on the Genetic-Inconsistent Paternity Cases Using the MiSeq FGx System

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