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Browsing Over 1843 Presentations
22P - Salicylidene Acylhydrazides attenuate SH-SY5Y neuroblastoma cell survival through mitotic regulator Speedy/RINGO and ERK/ MAPK - PI3K/ AKT pathways
- Ozgur Tanriverdi (Mugla, Turkey)
Abstract
Background
Iron is an essential element for cell proliferation, growth and cellular activities. Iron has been shown to be important for tumorigenesis and metastasis. Therefore, targeting the metabolic pathways of iron can provide new tools for cancer treatment. In this study, effects of iron chelating ME0053, ME0055 and ME0192 salicylidene acylhydrazides were investigated in SH-SY5Y cells. By targeting iron in the cell, iron chelators are known to act on cyclins and CDKs, as well as on AKT and MAPK signaling which function in tumorigenesis. Therefore, in this study the effect of used iron chelators on cell viability was investigated both on MAPK and AKT signaling and on the mitotic Speedy/RINGO protein, which potentially regulates the communication of these two signaling paths. In addition, the apoptotic states of the cells were examined by active caspase-3 analysis.
Methods
Appropriate administration dose of the ME053, ME055 and ME0192 compounds was determined by MTT analysis and SH-SY5Y cells were treated with these compounds. Then, the effect of iron chelators on Speedy/RINGO expression, AKT and MAPK signaling and also on the apoptotic state of cells were determined by western blotting.
Results
These compounds have been shown to reduce the phosphorylation level of AKT, one of the signaling molecules associated with survival in SH-SY5Y cells. A relatively less but significant decrease in the activity of the MAPK signaling was observed. Besides, it has been demonstrated for the first time that Speedy/RINGO protein expression was significantly reduced by these compounds with an yet unknown mechanism. Finally, the active caspase-3 analysis in SH-SY5Y cells showed that the compounds ME0053, ME0055 and ME0192 increased the amount of active caspase-3 by 218%, 90% and 175%, respectively.
Conclusions
It was shown for the first time that ME0053, ME0055 and ME0192 compounds showed a suppressive effect on the MAPK and AKT pathways, and also on the anti-apoptotic protein Speedy/RINGO, thereby causing apoptotic death of SH-SY5Y cells.
Legal entity responsible for the study
The authors.
Funding
This work was supported by grant from the Mugla Sitki Kocman University Scientific Research Project Office (Project No: 17/023).
Disclosure
All authors have declared no conflicts of interest.
23P - DAB2IP inhibits metastasis in NSCLC by governing cell-matrix and cell-cell adhesions
- Shenglan Yang (Chongqing, China)
Abstract
Background
Metastasis is a critical factor for the high mortality in Non-small-cell lung carcinoma (NSCLC), but the mechanism is still not completely understood. DAB2IP, as a Ras GTPase-activating protein and novel scaffold protein, is involved in the progression of various cancers. Previously, it was reported that DAB2IP methylation status in circulating DNA could predict response to erlotinib in EGFR-mutated NSCLC patients. However, the role of DAB2IP in NSCLC has rarely been investigated.
Methods
We collected 148 paraffin embedding tissues from primary NSCLC without distant metastases, and analyzed the relationship between DAB2IP and clinical pathology. We also used a lentivirus system to build the stable DAB2IP knockdown cell line A549-KD and compared the metastatic ability
Results
In 148 patients, regional metastases were found in 96 patients. In 96 patients with metastases, no or low-expression of DAB2IP was observed in a high number of patients (79 no or low/96 patients; 17 high/96 patients), while high expression was frequently detected in patients without metastasis (8 no or low/52 patients; 44 high/52 patients). This suggests that loss of DAB2IP could indicate the occurrence of metastases in lung cancer patients(p<0.0001). The patients with high expression of DAB2IP also had longer disease-free survival after surgery (p=0.013).
Conclusions
In summary, our study identified that DAB2IP has a role in predicting metastasis and poor survival in NSCLC. DAB2IP could regulate metastasis by governing cell-matrix and cell-cell adhesion.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
24P - Identification of Zfp161 as a regulator of the c-Myc oncogene in human cells
- Yening Feng (Rochester, United States of America)
Abstract
Background
Deregulated expression of the c-Myc oncogene is an important molecular hallmark of cancer. Previous studies have shown that the murine zinc finger protein ZF5 is a putative transcriptional regulator of c-Myc and can affect cell growth in mouse cell lines. The human zinc finger protein ZFP161 is 98% homologous to murine ZF5. The human gene Zfp161 is localized to 18p11.21 and cDNA of the gene has an open reading frame of 1347bp. We tested the regulatory effects of ZFP161 on c-Myc in human cells.
Methods
Correlation of Zfp161 and Myc in human colon cancer cells was derived from the R2 database. A Zfp161 knockout Hct116 cell line was prepared. Hct116 cells were transfected with PLK01, ZFP161 60shRNA and ZFP161 50shRNA to make Zfp161 knockdown cells. Western blot analysis was performed to determine ZFP161 and c-MYC protein levels in wild type Hct116 cells, Zfp161 knockout cells, control cells, 60sh-Zfp161 cells and in 50sh-Zfp161 cells. To test Zfp161 expression in the same cells, quantitative PCR (qPCR) analysis was performed. Clonogenic assays of 5 different cell types
Results
Western blots demonstrated decreased levels of ZFP161 protein in Zfp161 knockout and shRNA knockdown cells. Simultaneously, decreased c-MYC protein levels were observed in Zfp161 knockout and shRNA knockdown cells compared with wild type and knockdown control cells. Using qPCR, decreased c-Myc RNA levels were observed in Zfp161 knockout cells compared to wildtype cells and decreased c-Myc RNA levels were observed in shRNA knockdown cells compared to control cells. Our results show that knockout and knowdown of Zfp161 results in a significant decrease in c-Myc expression in human cells. The decrease of c-Myc in Zfp161 knockout and knockdown cells translated into a robust decrease of
Conclusions
Zfp161 is a regulator of the c-Myc oncogene in human cells. Zfp161 knockout and knowdown cells show a robust decrease of cell survival
Legal entity responsible for the study
Zhenkun Lou.
Funding
Mayo Clinic.
Disclosure
All authors have declared no conflicts of interest.
25P - The role of Speedy/RINGO in between MAPK and AKT pathways in SH-SY5Y neuroblastoma cells
- Ozgur Tanriverdi (Mugla, Turkey)
Abstract
Background
Triggering and overactivation of extracellular signal-regulated kinases/mitogen-activated protein kinase(MAPK) and phosphatidylinositol 3-kinase/protein kinase B(AKT) signaling pathways are one of the most important factors in the formation of many types of cancer, including neuroblastoma, by reducing the effectiveness of treatment and contributing to development of resistance to chemotherapy during the treatment process. There is evidence reinforcing the possibility that these two signaling pathways are communicating and interacting with each other in carcinogenic process. Yet it is unknown what is there at the heart of this interaction. There are studies giving insights about certain cell cycle regulators such as Speedy/RINGO which may be involved in the intersection of these signaling pathways. In these studies, connection of Speedy/RINGO with AKT and MAPK pathways is studied partially and also these studies are performed with cell and tissue types other than neuroblastoma. Thus, to date there is not any data available showing the connective role of Speedy/RINGO in between AKT and MAPK pathways and the aim of this study is to show the connective role of Speedy/RINGO between AKT and MAPK pathways in neuroblastoma cells.
Methods
In this study, MAPK pathway was firstly inhibited with U0126 chemical and expression of Speedy/RINGO was analyzed. A corresponding decrease in the expression of Speedy/RINGO and phosphorylation of AKT were shown. This data was confirmed with siRNA silencing of Speedy/RINGO.
Results
Showed that Speedy/RINGO inhibition caused a significant decrease in CyclinA and CDK2 expression levels and AKT phosphorylation amounts. It has also shown that these inhibition treatments significantly reduce the viability of cancer cells.
Conclusions
All data obtained from this study provide crucial information for the first time about the connecting and overactivating function of Speedy/RINGO in between AKT and MAPK pathways, thereby giving insights to choose appropriate molecular targets for diagnosis and treatment of many cancer types.
Legal entity responsible for the study
The authors.
Funding
This work was supported by the Scientific Research Project Office of Mugla Sitki Kocman University (Project Numbers 17/251 and 17/023).
Disclosure
All authors have declared no conflicts of interest.
26P - Coexpression of E- and N-cadherins as a sign of epithelial-mesenchymal transition (EMT) in prostate cancer (PCa)
- Marina Puchinskaya (Minsk, Belarus)
Abstract
Background
EMT is a process important for malignant tumor metastasis and drug resistance. Various molecules have been studied as markers of EMT, but still none of them can readily define cells more capable of aggressive behaviour. Expression of various markers differs in cancer cells. Several experimental works have shown that simultaneous presence of both epithelial and mesenchymal markers is important for metastasis. We aimed to assess coexpression of E- and N-cadherins (cad) in PCa cells as a sign of EMT.
Methods
A training cohort of PCa samples was stained using double immunofluorescence (dIF) technique. 4 μm thick slides of tissues obtained during radical prostatectomy were used for staining. Primary antibodies to E-cad (BioGenex, 1:150 dilution) and N-cad (ThermoFischerScientific, 1:1500) and secondary antibodies (ThermoFischerScientific, 1:200) conjugated with Alexa Fluor 488 and 555 probes were applied. Slides were studied using Nikon 5500 microscope. Patterns of markers coexpression were assessed.
Results
Staining pattern of both cadherins was predominantly membranous with entire membranes being stained in cancer cells, in some cases cytoplasmic staining was also seen. E-cad staining was homogenous and present in both non-cancerous glands (NCG) and PCa (down-regulated to different extent in the latter). Opposingly, N-cad staining was very patchy, the marker being present in only few cells, also both in PCa and NCG, in some cases staining in the latter was even more prominent. Either entire gland or only some cells were stained. Staining intensity was strong to moderate. As there were no cells with E-cad absence, cadherins co-expression was seen in all N-cad-positive cells and the percentage of coexpressing cells was, correspondingly, the same as N-cad+ cells. No significant signs of stronger E-cad down-regulation in N-cad positive cells compared to adjacent N-cad-negative was noted. Coexpression of cadherins was seen in <5% of PCa cells in 75% of cases.
Conclusions
Coexpression of epithelial and mesenchymal cadherins in PCa is dependent on N-cad expression that was present in a limited number of cells. It can be speculated that these rare cells are the main source of further PCa progression and metastasis.
Legal entity responsible for the study
M. Puchinskaya.
Funding
Belarusian Republican Foundation for Fundamental Research.
Disclosure
All authors have declared no conflicts of interest.
27P - Laryngopharyngeal reflux affects tumour immune microenvironment in carcinoma of larynx
- Yaroslav Kizim (Kyiv, Ukraine)
Abstract
Background
One of the risk factors of laryngeal cancer (LC), besides human papillomavirus (HPV) and smoking, is laryngopharyngeal reflux (LPR), which rate has been progressively rising worldwide. LPR is associated with low pH that can affect tumor immune microenvironment (TIME) in patients with LC. However, little is known about the effect of LPR on the TIME in LC. The goal of the study was to assess the impact of LPR on TIME of tumor infiltrating T-lymphocytes and macrophages in LC.
Methods
A total of 63 males with HPV-negative pT1-2 squamous cell LC were enrolled in the study. According to the results of 24-h pH monitoring, patients were subdivided into two groups: without (the 1st group, 30 patients) and with coexisting LPR (the 2nd group, 33 patients). TIME was assessed immunohistochemically by counting the number of T-lymphocytes (CD3), T-cytotoxic cells (CD8) and T-regulatory cells (Treg; FOXP3), M1 (CD68) and M2 macrophages (CD163) in the tumor and in the intact mucosa (IM) of the larynx taken from the tumor-negative margins.
Results
LC with coexisting LPR demonstrated higher inflammatory infiltration of tumors and IM than in patients without LPR. However, no statistically significant differences were found between the number of CD3+ and CD8+ cells within LC of the 1st and 2nd groups though density of CD3 cells in IM was higher in the 2nd group (P=0.003). In contrast, LPR was associated with increased amount of immunosuppressive Treg cells (P=0.008). In addition, numerous CD68+ macrophages were found within LC of both groups. However, M2 macrophages density was much higher in LC (P<0.001) and IM (P=0.021) of the 2nd group patients. A negative correlation between pH values obtained during pH monitoring and number of tumor-associated CD163-positive macrophages (r=0.71; P<0.001) supports the association between LPR-related milieu acidity and M2-macrophages polarization in LC.
Conclusions
LPR causes chronic inflammation in the laryngeal mucosa and alters the TIME in LC, facilitating M2-macropheges polarization and increasing Treg cells number that can impact tumor biological behavior and immune escape mechanisms.
Legal entity responsible for the study
Kolomiychenko Institute of Otolaryngology of NAMS of Ukraine.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
28P - Frequency and spectrum of founder and non-founder BRCA1/2 mutations in a large series of Russian breast cancer and ovarian cancer patients
- Tatiana N. Sokolova (Saint-Petersburg, Russian Federation)
Abstract
Background
The spectrum of
Methods
We analyzed a large data set of Russian breast cancer (BC) and ovarian cancer (OC) patients, who were subjected to founder mutation tests or full-length
Results
The most commonly applied test, which included 4 founder mutations (
Conclusions
Full-length
Legal entity responsible for the study
The authors.
Funding
The study was supported by the Russian Foundation for Basic Research [grant numbers 20-515-00002].
Disclosure
All authors have declared no conflicts of interest.
29P - Genomic features of Chinese lung squamous cell carcinoma patients
- Zhongquan Zhao (Fuzhou, China)
Abstract
Background
Despite the achievements made in treating lung cancer during the past decades, lung cancer remains the leading carcinoma of incidence and death rates world widely. Compared to lung adenocarcinoma, the genomic features of Chinese lung squamous cell carcinoma (SQCC) have not been well established yet.
Methods
We enrolled 488 Chinese SQCC patients in this study from 2017 to 2020. All samples were subjected to next-generation sequencing assay of 14 major lung cancer-related genes, involving
Results
Of 488 patients with SQCC, 444 (90.98%) were proved to have at least one alteration in the 14 lung cancer-related genes. Compared with the Cancer Genome Atlas (TCGA) data base, a significant higher mutated frequency was found in
Conclusions
Our study identified a unique genomic feature of Chinese SQCC patients by next-generation sequencing and provided new insights on the relationship between driver genes and PD-L1 expression.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
30P - The prevalence of loss of heterozygosity at human leukocyte antigen locus in Chinese cancer patients
- Taiyan Yu (Kunming, China)
Abstract
Background
Human leukocyte antigen (HLA) is a gene complex encoding major histocompatibility complex (MHC) proteins. HLA-A, HLA-B, and HLA-C are three main HLA class I genes that present peptides to cell surface, leading immune system to destroy the cells. Loss of heterozygosity (LOH) at HLA locus reduces the capacity of neoantigen presentation, thereby aiding immune evasion of tumors.
Methods
We developed an HLA typing method based on a Bayesian classification algorithm called Polysolver, which deciphers HLA type from 539-gene panel genomic data by next-generation sequencing. The method was validated on samples with the standard PCR-SBT (sequencing-based typing) results. HLA-LOH was determined by comparing HLA typing results between paired tumor and white blood cell samples. We performed the HLA typing and HLA-LOH analysis on 1342 real-world clinical samples across 17 cancer types, mostly lung cancer (LC), liver cancer (HCC), and colorectal cancer (CRC).
Results
Within all 1342 samples, 279 (20.8%) carried at least one homozygous HLA gene, which indicates that most individuals with no homozygous HLA gene may benefit better from targeted therapies than others, according to previous studies. LOH results (on HLA-A, HLA-B, and HLA-C) were available in 524 FFPE samples with at least 50% tumor ratio (H&E stain). Within the 524 samples, 118 (22.5%) carried at least one LOH gene, in which LC had the highest LOH ratio (25.8%, 41/159) among different cancer types. Among all samples with HLA-LOH, more than 50% of them had all three genes with LOH, suggested that the three genes tended to be lost at the same time. Patients with LOH gene had significantly higher TMB than patients without LOH gene (mean TMB: 6.57 vs. 5.19, p = 0.0003). LOH ratio is significantly higher in elder patients (28.0%, 63/225, age above 60) than younger patients (13.18%, 11/80, age below 40), suggested that immunotherapy may be less responded in elder patients. No significant correlation was found between LOH ratio and PD-L1 expression.
Conclusions
We established an accurate HLA typing method and investigated the prevalence of HLA typing and HLA-LOH in Chinese cancer patients, which may provide references and insights for further immunotherapy research.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
31P - Accurate detection of HRD status in multiple cancer types using somatic mutation pattern
- Chengcheng D. Zhou (Beijing, China)
Abstract
Background
Homologous Recombination Deficiency (HRD) is caused by various molecular alterations in genes that participate in HR repair. However, HR is a complicated biological process and it is unlikely that all HRD causing alterations have been uncovered so far. We hypothesized that HRD detection based on mutation pattern can accurately detect HRD status with better patient stratification.
Methods
We retrieved mutations of ovarian cancer from TCGA repository. Samples treated with platinum chemotherapy were selected for further analysis. Mutation pattern were profiled using negative matrix factorization (NMF) method. Samples were tiered based on weight of HRD-related mutation signature. Cox model was applied to compare survival of samples of each tier against non-HRD samples separately. To test the feasibility of our method on targeted sequencing data, mutation profile was shrunk to selected genomic region composed of 825 genes (∼ 2.2Mb). We retrieved 192 in-house clinical samples and labeled HRD status based on known HRD causing variants. We applied our method on these samples to inspect the consistency.
Results
375 samples were profiled for HRD status and were divided into four tiers based on the weight of HRD-related mutation pattern. Cox model showed significant survival difference (p-value = 0.001) proportional to the weight of HRD mutation pattern with higher weight being the longest survival and vice versa. 223 and 152 samples were categorized as HRD and non-HRD based on optimized threshold and survival difference remains significant (p-value = 0.0017). Similar survival difference was observed (p-value=0.0013) suggesting the validity of the method on targeted sequencing. Out of 124, 49 and 19 breast, ovarian and prostate cancer samples, 13, 11 and 4 of them were labeled as HRD positive based on known HRD causing variants. All but one HRD positive samples were consistently classified by our method.
Conclusions
Our results showed that NMF method is able to faithfully detect HRD samples. The method can be applied to WES as well as targeted sequencing and achieve equally significant survival difference between samples with different HR status. Upon detecting HRD, this method can identify additional HRD patients and therefore make better patient stratification.
Legal entity responsible for the study
Beijing Genetron Health Genetic Technology Co., Ltd.
Funding
Beijing Genetron Health Genetic Technology Co. Ltd.
Disclosure
All authors have declared no conflicts of interest.
32P - Comparison of fully automated microsatellite instability test to immunohistochemistry for mismatch repair protein expression in endometrial carcinoma
- Marta Mendiola (Madrid, Spain)
Abstract
Background
Endometrial cancer (EC) is the most prevalent amongst gynaecological malignancies, and microsatellite instability (MSI), has been reported in up to 30% of cases. This is mainly caused by alteration of DNA mismatch repair (MMR) genes and can be explored by loss of MMR proteins expression by immunohistochemistry (IHC), or alternatively, by MSI status.
Methods
Firstly, 276 early stage low grade (G1-G2) EC patients were classified by IHC by evaluation of tissue microarrays. Based on the expression of MLH1, PMS2, MSH2 and MSH6, samples were classified as MMR-proficient (MMR-p; all four proteins retained expression) or deficient (MMR-d; one or more proteins showed loss of expression). Secondly, the Idylla™ MSI Test (Idylla™), was used to retest DNA from all MMR-d cases and a random selection of an approximately equal number of MMR-p cases. Non-informative cases by IHC were also retested by Idylla™.
Results
A total of 276 EC were analysed by IHC; 30 (11%) samples were not initially informative, 35 (13%) samples were classified as MMR-d, and 211 (77%) as MMR-p. Idylla™ was able to rescue 29/30 (97%) of the non-informative IHC samples. 23/29 (79%) were determined as Microsatellite Stable (MSS) and 6/29 (21%) as MSI-High (MSI-H). In the MMR-d group, 16 out of 35 samples were equally classified, but the other 19 were classified as MSS, showing a discrete sensitivity compared to IHC (45.71%). Within the 44 MMR-p randomly selected samples, all were identically classified by Idylla™ except one, that was classified as MSI-H by Idylla™, showing high specificity compared to IHC (97.72%). Overall, there is a concordance of 74.68% between IHC and Idylla™.
Conclusions
This preliminary data show that the Idylla™ MSI Test is able to rescue the majority of samples which are classified as non-informative using IHC and that the Idylla™ MSI Test seems to be highly correlated with IHC in the identification of MMR-p EC cases, but a substantial lower concordance rate has been observed for the MMR-d EC cases. Further analyses have to be performed to explain the observed discordances of these MMR-d cases.
Legal entity responsible for the study
Hospital Universitario la Paz-IdiPAZ.
Funding
Biocartis NV.
Disclosure
M. Mendiola: Non-remunerated activity/ies, research collaboration: Biocartis; Honoraria (self), speaker: AstraZeneca; Honoraria (self), speaker: Tesaro. A. Gallego Martínez: Advisory/Consultancy: Pharmamar; Travel/Accommodation/Expenses: Pharmamar; Speaker Bureau/Expert testimony: Clovis; Speaker Bureau/Expert testimony: AstraZeneca; Speaker Bureau/Expert testimony: MSD; Travel/Accommodation/Expenses: MSD; Travel/Accommodation/Expenses: Tesaro (GSK); Travel/Accommodation/Expenses: Pierre-Fabre; Non-remunerated activity/ies, Non remunerated membership: SEOM; Non-remunerated activity/ies, Non remunerated membership: GEICO; Non-remunerated activity/ies, Non remunerated membership: European Orgnisation Treatment Throphoblastic disease; Non-remunerated activity/ies, Non remunerated membership: ESMO. D. Hardisson: Non-remunerated activity/ies, Principal investigator, Molecular Pathology and Therapeutic Targets Lab: IdiPAZ. A. Redondo: Honoraria (self), Research grant/Funding (self), speaker and advisory role: Roche; Honoraria (self), Research grant/Funding (institution), speaker and advisory role: Pharmamar; Honoraria (self), speaker and advisory role: AstraZeneca; Honoraria (self), speaker and advisory role: GSK; Honoraria (self), speaker and advisory role: Clovis; Honoraria (self), speaker: Novartis; Honoraria (self), Advisory role: Amgen; Research grant/Funding (institution): Roche; Research grant/Funding (institution): Eisai; Non-remunerated activity/ies, Member of executive board and secretary: GEICO; Non-remunerated activity/ies, PI of phase II Cecilia study sponsored by Roche: Roche. All other authors have declared no conflicts of interest.
33P - BLAST-guided mappability knowledgebase facilitates accurate detection of somatic variants
- Shuang Wang (Beijing, China)
Abstract
Background
In NGS data analysis, when nucleotide polymorphisms (SNPs) exist within genomic region of low mappability, misalignments can raise alone with additional mismatches that may be identified as somatic variants. Due to the nature of SNPs between individual, no modern variant caller can algorithmically distinguish artifacts of such origin. A pre-indexed knowledgebase may help distinguishing such artifacts from real somatic variants.
Methods
The goal is to construct a knowledgebase of genomic regions that characterize as low mappable while highly polymorphic. We generated a synthetic data by dividing human reference genome into reads with length of 300bp and step of 75bp. BLAST was then used to search for region of similarity between FASTA and reference genome and preliminary inclusion criterion of similarity region was set. To validate artifacts of hypothesized origin, we generated another FASTA file by inserting SNPs of NA18595 from 1KGP into original FASTA file. The FASTA was aligned to reference genome so that the origin of mismatches can be explored.
Results
As expected, no mismatches were detected when synthetic data is free of SNPs. After germline variants were inserted, a total amount of 91 mismatches were identified at exome scale. All artifacts raised from reads that harbored SNPs and were misaligned to genomic regions of similar sequence context. Out of 91 artifacts, 36% occurred at very SNPs loci and 58% of them occurred at loci adjacent to SNPs. 94% artifacts were covered by our artifact knowledgebase. In addition, 59% of potential artifacts in our knowledgebase were reported in COSMIC. Although this only provided a rough estimation since we only selected artifact sites adjacent to polymorphic site of high population frequency (>5%), this high percentage implies the existence of artifacts in public cancer mutation knowledgebase.
Conclusions
Our analysis indicates that the difference between reference and individual can lead to misalignment especially when such genomic polymorphism occurs within low mappable regions. These misalignments may introduce false somatic variants. By constructing a BLAST-guided knowledgebase, we were able to faithfully detect artifact of such origin and achieve higher specificity of somatic variant detection.
Legal entity responsible for the study
Genetron Health (Beijing) Co. Ltd., 102206, Beijing, China.
Funding
Genetron Health (Beijing) Co. Ltd., 102206, Beijing, China.
Disclosure
All authors have declared no conflicts of interest.