scholarly journals Open-Sourced CIViC Annotation Pipeline to Identify and Annotate Clinically Relevant Variants Using Single-Molecule Molecular Inversion Probes

2019 ◽  
pp. 1-12 ◽  
Author(s):  
Erica K. Barnell ◽  
Adam Waalkes ◽  
Matt C. Mosior ◽  
Kelsi Penewit ◽  
Kelsy C. Cotto ◽  
...  
Keyword(s):  
Single Molecule ◽  
Annotation Pipeline ◽  
Patients With Cancer ◽  
Open Access Database ◽  
Design Paradigm ◽  
Molecular Inversion Probes ◽  
Sequencing Platforms ◽  
Tumor Types ◽  
Molecular Inversion Probe ◽  
Actionable Variants

PURPOSE Clinical targeted sequencing panels are important for identifying actionable variants for patients with cancer; however, existing approaches do not provide transparent and rationally designed clinical panels to accommodate the rapidly growing knowledge within oncology. MATERIALS AND METHODS We used the Clinical Interpretations of Variants in Cancer (CIViC) database to develop an Open-Sourced CIViC Annotation Pipeline (OpenCAP). OpenCAP provides methods to identify variants within the CIViC database, build probes for variant capture, use probes on prospective samples, and link somatic variants to CIViC clinical relevance statements. OpenCAP was tested using a single-molecule molecular inversion probe (smMIP) capture design on 27 cancer samples from 5 tumor types. In total, 2,027 smMIPs were designed to target 111 eligible CIViC variants (61.5 kb of genomic space). RESULTS When compared with orthogonal sequencing, CIViC smMIP sequencing demonstrated a 95% sensitivity for variant detection (n = 61 of 64 variants). Variant allele frequencies for variants identified on both sequencing platforms were highly concordant (Pearson’s r = 0.885; n = 61 variants). Moreover, for individuals with paired tumor and normal samples (n = 12), 182 clinically relevant variants missed by orthogonal sequencing were discovered by CIViC smMIP sequencing. CONCLUSION The OpenCAP design paradigm demonstrates the utility of an open-source and open-access database built on attendant community contributions with peer-reviewed interpretations. Use of a public repository for variant identification, probe development, and variant interpretation provides a transparent approach to build dynamic next-generation sequencing–based oncology panels.

scholarly journals Identification of community-consensus clinically relevant variants and development of single molecule molecular inversion probes using the CIViC database

2018 ◽  
Author(s):  
Erica K. Barnell ◽  
Adam Waalkes ◽  
Kelsi Penewit ◽  
Katie M. Campbell ◽  
Zachary L. Skidmore ◽  
...  
Keyword(s):  
Single Molecule ◽  
Pearson Correlation ◽  
Genomic Region ◽  
Variant Annotation ◽  
Design Paradigm ◽  
Molecular Inversion Probes ◽  
Sequencing Platforms ◽  
Tumor Types ◽  
Molecular Inversion Probe ◽  
Actionable Variants

AbstractClinical targeted sequencing panels are important for identifying actionable variants for cancer patients, however, there are currently no strategies to create impartial and rationally-designed panels to accommodate rapidly growing knowledge within the field. Here we use the Clinical Interpretations of Variants in Cancer database (CIViC) in conjunction with single-molecule molecular inversion probe (smMIP) capture to identify and design probes targeting clinically relevant variants in cancer. In total, 2,027 smMIPs were designed to target 111 eligible CIViC variants. The total genomic region covered by the CIViC smMIPs reagent was 61.5 kb. When compared to existing genome or exome sequencing results (n = 27 cancer samples from 5 tumor types), CIViC smMIP sequencing demonstrated a 95% sensitivity for variant detection (n = 61/64 variants). Variant allele frequency for variants identified on both sequencing platforms were highly concordant (Pearson correlation = 0.885; n = 61 variants). Moreover, for individuals with paired tumor/normal samples (n = 12), 182 clinically relevant variants missed by original sequencing were discovered by CIViC smMIPs sequencing. This design paradigm demonstrates the utility of an open-sourced database built on attendant community contributions for each variant with peer-reviewed interpretations. Use of a public repository for variant identification, probe development, and variant annotation could provide a transparent approach to build a dynamic next-generation sequencing–based oncology panel.

scholarly journals Genome-Wide Identification of 5-Methylcytosine Sites in Bacterial Genomes By High-Throughput Sequencing of MspJI Restriction Fragments

2021 ◽  
Author(s):  
Brian P. Anton ◽  
Alexey Fomenkov ◽  
Victoria Wu ◽  
Richard J. Roberts
Keyword(s):  
Single Molecule ◽  
Dna Sequences ◽  
High Throughput Sequencing ◽  
Cost Effective ◽  
Restriction Enzymes ◽  
Specific Sequence ◽  
Genome Wide ◽  
Cost Effective Alternative ◽  
Simple Column ◽  
Sequencing Platforms

ABSTRACTSingle-molecule Real-Time (SMRT) sequencing can easily identify sites of N6-methyladenine and N4-methylcytosine within DNA sequences, but similar identification of 5-methylcytosine sites is not as straightforward. In prokaryotic DNA, methylation typically occurs within specific sequence contexts, or motifs, that are a property of the methyltransferases that “write” these epigenetic marks. We present here a straightforward, cost-effective alternative to both SMRT and bisulfite sequencing for the determination of prokaryotic 5-methylcytosine methylation motifs. The method, called MFRE-Seq, relies on excision and isolation of fully methylated fragments of predictable size using MspJI-Family Restriction Enzymes (MFREs), which depend on the presence of 5-methylcytosine for cleavage. We demonstrate that MFRE-Seq is compatible with both Illumina and Ion Torrent sequencing platforms and requires only a digestion step and simple column purification of size-selected digest fragments prior to standard library preparation procedures. We applied MFRE-Seq to numerous bacterial and archaeal genomic DNA preparations and successfully confirmed known motifs and identified novel ones. This method should be a useful complement to existing methodologies for studying prokaryotic methylomes and characterizing the contributing methyltransferases.

scholarly journals Full-Length Transcriptome Sequences by A Combination of Sequencing Platforms Applied to Isoflavonoid and Triterpenoid Saponin Biosynthesis of Astragalus Mongholicus Bunge

2020 ◽  
Author(s):  
Minzhen Yin ◽  
Shanshan Chu ◽  
Tingyu Shan ◽  
Liangping Zha ◽  
Huasheng Peng
Keyword(s):  
Single Molecule ◽  
Molecular Genetic ◽  
Gene Families ◽  
Triterpenoid Saponin ◽  
Smrt Sequencing ◽  
Triterpenoid Saponins ◽  
Saponin Biosynthesis ◽  
Medicinal Value ◽  
Long Time ◽  
Sequencing Platforms

Abstract Background: Astragalus mongholicus Bunge is an important medicinal plant and has been used in traditional Chinese medicine for a long history, which is rich in isoflavonoids and triterpenoid saponins. Although these active constituents in A. mongholicus have been discovered for a long time, the molecular genetic basis of the isoflavonoid and triterpenoid saponin biosynthesis pathways is virtually unknown due to the lack of a reference genome. The combination of next-generation sequencing (NGS) and single-molecule real-time (SMRT) sequencing to analyze genes involved in the biosynthetic pathways of secondary metabolites in medicinal plants has been widely recognized.Results: In this study, NGS, SMRT sequencing, and targeted compounds were combined to investigate the association between isoflavonoids and triterpenoid saponins and gene expression in roots, stems and leaves of A. mongholicus. A total of four main isoflavonoids and four astragalosides (belong to triterpenoid saponins) were measured, and 44 differentially expressed genes (DEGs) of nine gene families, 44 DEGs of 16 gene families that encode for enzymes involved in isoflavonoid and triterpenoid saponin biosynthesis were identified, separately. Additionally, transcription factors (TFs) associated with isoflavonoid and triterpenoid saponin biosynthesis were analyzed, including 72 MYBs, 53 bHLHs, 64 AP2-EREBPs and 11 bZIPs. The above transcripts exhibit different expression trends in different organs.Conclusions: Our study provides important genetic information for the essential genes of isoflavonoid and triterpenoid saponin biosynthesis in A. mongholicus, and provides a basis for developing its medicinal value.

scholarly journals Genome-wide identification of 5-methylcytosine sites in bacterial genomes by high-throughput sequencing of MspJI restriction fragments

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0247541
Author(s):  
Brian P. Anton ◽  
Alexey Fomenkov ◽  
Victoria Wu ◽  
Richard J. Roberts
Keyword(s):  
Single Molecule ◽  
Dna Sequences ◽  
High Throughput Sequencing ◽  
Cost Effective ◽  
Restriction Enzymes ◽  
Specific Sequence ◽  
Genome Wide ◽  
Cost Effective Alternative ◽  
Simple Column ◽  
Sequencing Platforms

Single-molecule Real-Time (SMRT) sequencing can easily identify sites of N6-methyladenine and N4-methylcytosine within DNA sequences, but similar identification of 5-methylcytosine sites is not as straightforward. In prokaryotic DNA, methylation typically occurs within specific sequence contexts, or motifs, that are a property of the methyltransferases that “write” these epigenetic marks. We present here a straightforward, cost-effective alternative to both SMRT and bisulfite sequencing for the determination of prokaryotic 5-methylcytosine methylation motifs. The method, called MFRE-Seq, relies on excision and isolation of fully methylated fragments of predictable size using MspJI-Family Restriction Enzymes (MFREs), which depend on the presence of 5-methylcytosine for cleavage. We demonstrate that MFRE-Seq is compatible with both Illumina and Ion Torrent sequencing platforms and requires only a digestion step and simple column purification of size-selected digest fragments prior to standard library preparation procedures. We applied MFRE-Seq to numerous bacterial and archaeal genomic DNA preparations and successfully confirmed known motifs and identified novel ones. This method should be a useful complement to existing methodologies for studying prokaryotic methylomes and characterizing the contributing methyltransferases.

scholarly journals Impact of ABO Blood Group Type on Risk of Venous Thromboembolism in Patients with Cancer

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2119-2119
Author(s):  
Cornelia Englisch ◽  
Florian Moik ◽  
Stephan Nopp ◽  
Markus Raderer ◽  
Ingrid Pabinger ◽  
...  
Keyword(s):  
Risk Factor ◽  
Blood Type ◽  
Thrombotic Risk ◽  
Patients With Cancer ◽  
Abo Blood Type ◽  
Tumor Types ◽  
Risk Of Cancer ◽  
Very High ◽  
Study Inclusion

Abstract Introduction: Venous thromboembolism (VTE) is common in patients with cancer. Non-O blood type is associated with higher levels of factor FVIII activity and von Willebrand factor compared to blood type O, and has been identified as a risk factor for VTE in the general population. However, the impact of ABO blood type on risk of cancer-associated VTE has not been clarified. Methods: To determine the influence of non-O blood type on risk of cancer-associated VTE, we utilized the dataset of the Vienna Cancer and Thrombosis Study (CATS), which is a single center, prospective observational cohort study including patients with newly diagnosed or recurrent cancer. Patients were followed for objectively diagnosed, independently adjudicated VTE for a maximum of 2 years. VTE was quantified in competing risk analysis, accounting for all-cause mortality as competing outcome event. A proportional sub-hazard regression model according to Fine & Gray was used for between-group comparisons. Based on the violation of the proportional sub-hazard assumption, we explored potential time-dependent effects of non-O blood type on VTE risk in a restricted cubic spline analysis, modeling differences in risk estimates over follow-up time. Further, time-restricted subdistribution hazard ratios (SHR) were obtained specifically for the <3 months and ≥3 months follow-up intervals. In a subgroup analysis, differences in VTE risk according to ABO-blood type were analyzed for patients with very high thrombotic risk tumor types (pancreatic, gastric, glioblastoma), compared to the remainder of patients. Results: In total, 1,708 patients were included in our analysis (46% female, median age: 61 years [interquartile range, IQR: 52-68]). The most common tumor types were lung (19%), breast (16%), and brain (14%) cancer, with 32% of solid tumor patients having metastatic disease at study inclusion. Over a median follow-up of 24 months (IQR: 10-24), 151 patients were diagnosed with VTE (cumulative 2-year incidence: 9.2%, 95% confidence interval [CI]: 7.9-10.7) and 649 patients died (2-year mortality: 38%). Overall, blood type O was present in 38% of patients, A in 40%, B in 15%, and AB in 7%. The cumulative incidence of VTE at 3-, 6-, 12-, and 24-months for patients with blood type O was 3.8% (95% CI: 2.5-5.5), 5.7% (95% CI: 4.1-7.7), 7.0% (95% CI: 5.1-9.1), and 7.6% (95% CI: 5.7-9.9), compared to 3.4% (95% CI: 2.4-4.7), 6.5% (95% CI: 5.1-8.1), 8.4% (95% CI:6.8-10.2), and 10.2% (95% CI: 8.4-12.2) in patients with non-O blood type (Gray´s test: p=0.103, Figure 1). Upon visual inspection of cumulative incidence functions, a violation of the proportional sub-hazard assumption was suspected. In restricted cubic spline analysis, estimating hazard ratio (HR) for VTE of patients with non-O compared to O blood type, a time-varying effect of non-O blood type towards an increased VTE risk was observed (Figure 2). Based on that, time-restricted competing risk regression models were performed. During the first 3 months of follow-up, no differences in VTE risk were found (SHR for non-O vs. O blood type: 1.00, 95% CI: 0.60-1.67, p=0.992). Beyond the first 3-month follow-up, patients with non-O blood type had an increased VTE risk compared to patients with blood type O (SHR 1.79, 95%CI: 1.12-2.85, p=0.015). In a subgroup analysis, no association with VTE risk was found in patients with very high thrombotic risk tumor types (SHR 0.94, 95% CI: 0.55-1.61, p=0.824). In contrast, in patients with low/intermediate risk cancer, non-O blood type was associated with increased risk of VTE (SHR 1.73, 95% CI: 1.09-2.73, p=0.019). Conclusion: Non-O blood type was identified as a time dependent risk factor for cancer-associated VTE. In the first 3 months after study inclusion, characterized as the highest VTE risk period in our cancer cohort, no differences in VTE risk between blood types were found. Afterwards, beyond the first 3 months of follow-up, an increased VTE-risk in non-O blood types was observed, comparably in magnitude to the risk difference in the general non-cancer population. Further, an association of non-O blood type with VTE risk in patients with low/intermediate thrombotic risk cancers was observed, whereas no effect was present in those with very high-risk tumors. These findings indicate non-O blood type as a putative risk factor for VTE in patients with cancer in comparably low thrombotic risk scenarios. Figure 1 Figure 1. Disclosures Pabinger: Pfizer: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Alexion: Consultancy, Honoraria; Daiichi Sanchyo: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Bayer: Consultancy, Honoraria; NovoNordisk: Consultancy, Research Funding; CSL Behring: Consultancy, Honoraria, Research Funding.

scholarly journals Neutralization breadth of SARS CoV-2 viral variants following primary series and booster SARS CoV-2 vaccines in patients with cancer

2021 ◽  
Author(s):  
Vivek Naranbhai ◽  
Kerri J St. Denis ◽  
Evan C Lam ◽  
Onosereme Ofoman ◽  
Wilfredo F Garcia-Beltran ◽  
...  
Keyword(s):  
Immune Responses ◽  
Primary Vaccination ◽  
High Antibody ◽  
Patients With Cancer ◽  
Primary Series ◽  
Vaccine Type ◽  
High Antibody Titer ◽  
Binding Antibody ◽  
Alpha Beta ◽  
Tumor Types

Patients with cancer are more likely to have impaired immune responses to SARS CoV-2 vaccines. We studied the breadth of responses against SARS CoV-2 variants followingly primary vaccination in 178 patients with a variety of tumor types, and after booster doses in a subset. Neutralization of alpha, beta, gamma and delta SARS-CoV-2 variants was impaired relative to wildtype (Wuhan), regardless of vaccine type. Regardless of viral variant, mRNA1273 was the most immunogenic, followed by BNT162b2 and then Ad26.COV2.S. Neutralization of more variants (breadth) was associated with higher magnitude of wildtype neutralization, and increase with time since vaccination; increased age associated with lower breadth. Anti-spike binding antibody concentrations were a good surrogate for breadth (PPV=90% at >1000U/ml). Booster SARS-CoV-2 vaccines conferred enhanced breadth. These data suggest that achieving a high antibody titer is desirable to achieve broad neutralization; a single booster dose with current vaccines increases breadth of responses against variants.

BRCA Testing by Single-Molecule Molecular Inversion Probes

2017 ◽  
Vol 63 (2) ◽  
pp. 503-512 ◽  
Author(s):  
Kornelia Neveling ◽  
Arjen R Mensenkamp ◽  
Ronny Derks ◽  
Michael Kwint ◽  
Hicham Ouchene ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Copy Number Variation ◽  
Single Molecule ◽  
Copy Number ◽  
Single Gene ◽  
Work Flow ◽  
Analytical Sensitivity ◽  
Brca1 And Brca2 ◽  
Number Variation ◽  
Molecular Inversion Probes

Abstract BACKGROUND Despite advances in next generation DNA sequencing (NGS), NGS-based single gene tests for diagnostic purposes require improvements in terms of completeness, quality, speed, and cost. Single-molecule molecular inversion probes (smMIPs) are a technology with unrealized potential in the area of clinical genetic testing. In this proof-of-concept study, we selected 2 frequently requested gene tests, those for the breast cancer genes BRCA1 and BRCA2, and developed an automated work flow based on smMIPs. METHODS The BRCA1 and BRCA2 smMIPs were validated using 166 human genomic DNA samples with known variant status. A generic automated work flow was built to perform smMIP-based enrichment and sequencing for BRCA1, BRCA2, and the checkpoint kinase 2 (CHEK2) c.1100del variant. RESULTS Pathogenic and benign variants were analyzed in a subset of 152 previously BRCA-genotyped samples, yielding an analytical sensitivity and specificity of 100%. Following automation, blind analysis of 65 in-house samples and 267 Norwegian samples correctly identified all true-positive variants (>3000), with no false positives. Consequent to process optimization, turnaround times were reduced by 60% to currently 10–15 days. Copy number variants were detected with an analytical sensitivity of 100% and an analytical specificity of 88%. CONCLUSIONS smMIP-based genetic testing enables automated and reliable analysis of the coding sequences of BRCA1 and BRCA2. The use of single-molecule tags, double-tiled targeted enrichment, and capturing and sequencing in duplo, in combination with automated library preparation and data analysis, results in a robust process and reduces routine turnaround times. Furthermore, smMIP-based copy number variation analysis could make independent copy number variation tools like multiplex ligation-dependent probes amplification dispensable.

Comprehensive genomic profiling to identify tumor mutational burden (TMB) as an independent predictor of response to immunotherapy in diverse cancers.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e14508-e14508 ◽  
Author(s):  
Aaron Goodman ◽  
Shumei Kato ◽  
Lyudmila Bazhenova ◽  
Sandip Pravin Patel ◽  
Garrett Michael Frampton ◽  
...  
Keyword(s):  
Strong Dependence ◽  
Multivariable Analysis ◽  
Favorable Outcome ◽  
Genomic Profiling ◽  
Outcome Parameters ◽  
Patients With Cancer ◽  
Comprehensive Genomic Profiling ◽  
Response Biomarker ◽  
Tumor Mutational Burden ◽  
Tumor Types

e14508 Background: Immunotherapy induces durable responses in a subset of patients with cancer. High TMB may be a response biomarker for PD-1/PD-L1 blockade in tumors such as melanoma and non-small cell lung cancer (NSCLC). Our aim was to examine the relationship between TMB and outcome in diverse cancers treated with various immunotherapies. Methods: We reviewed data on 1,638 patients who had undergone comprehensive genomic profiling and had TMB assessment. Immunotherapy-treated patients (N = 151) were analyzed for response rate (RR), progression-free and overall survival (PFS, OS). Results: Higher TMB was independently associated with better outcome parameters (multivariable analysis). The RR for patients with high (≥ 20 mutations/mb) vs. low to intermediate TMB was 22/38 (58%) vs. 23/113 (20%) (P = 0.0001); median PFS, 12.8 vs. 3.3 months (P = <0.0001); median OS, not reached vs. 16.3 months (P = 0.0036) (Table). Results were similar when anti-PD-1/PD-L1 monotherapy was analyzed (N = 102 patients), with a linear correlation between higher TMB and favorable outcome parameters; the median TMB for responders vs. non-responders treated with anti-PD-1/PD-L1 monotherapy was 18.0 vs. 5.0 mutations/mb (P < 0.0001). Comparable data was observed when patients with melanoma (N = 52) and NSCLC (N = 36) were excluded (N = 63 patients; 19 tumor types). Interestingly, anti-CTLA4/anti-PD-1 combinations vs. anti-PD-1/PD-L1 monotherapy was selected as a factor independent of TMB for predicting better RR (77% vs. 21%) (P = 0.004) and PFS (P = 0.024). Conclusions: Higher TMB predicts favorable outcome to PD-1/PD-L1 blockade across diverse tumors. Benefit from dual checkpoint blockade did not show a similarly strong dependence on TMB. [Table: see text]

scholarly journals Immune Regulation of Cancer

2010 ◽  
Vol 28 (29) ◽  
pp. 4531-4538 ◽  
Author(s):  
Mary L. Disis
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Adaptive Immune System ◽  
Tumor Stroma ◽  
Tissue Destruction ◽  
Cancer Proliferation ◽  
Patients With Cancer ◽  
Adaptive Immune ◽  
Improved Outcomes ◽  
Tumor Types

Innate and adaptive immune system cells play a major role in regulating the growth of cancer. Although it is commonly thought that an immune response localized to the tumor will inhibit cancer growth, it is clear that some types of inflammation induced in a tumor may also lead to cancer proliferation, invasion, and dissemination. Recent evidence suggests, however, that some patients with cancer can mount an antitumor immune response that has the potential to control or eliminate cancer. Indeed, a so-called “immune response” signature has been described in malignancy that is associated with improved outcomes in several tumor types. Moreover, the presence of specific subsets of T cells, which have the capability to penetrate tumor stroma and infiltrate deep into the parenchyma, identifies patients with an improved prognosis. Immune-based therapies have the potential to modulate the tumor microenvironment by eliciting immune system cells that will initiate acute inflammation that leads to tissue destruction.

D-Dimer and Prothrombin Fragment 1 + 2 Predict Venous Thromboembolism in Patients With Cancer: Results From the Vienna Cancer and Thrombosis Study

2009 ◽  
Vol 27 (25) ◽  
pp. 4124-4129 ◽  
Author(s):  
Cihan Ay ◽  
Rainer Vormittag ◽  
Daniela Dunkler ◽  
Ralph Simanek ◽  
Alexandru-Laurentiu Chiriac ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Multivariable Analysis ◽  
High Grade Glioma ◽  
Cumulative Probability ◽  
Total Study Population ◽  
Prothrombin Fragment ◽  
Patients With Cancer ◽  
Progression Of Disease ◽  
Tumor Types ◽  
D Dimer

Purpose Venous thromboembolism (VTE) is a well-recognized complication of cancer. Laboratory parameters might be useful to assess the VTE risk in patients with cancer. The aim of this study was to investigate D-dimer and prothrombin fragment 1 + 2 (F 1 + 2), which reflect activation of blood coagulation and fibrinolysis, for prediction of cancer-associated VTE. Patients and Methods In a prospective, observational, cohort study of 821 patients with newly diagnosed cancer or progression of disease who did not recently receive chemotherapy, radiotherapy, or surgery were enrolled and followed for a median of 501 days (interquartile range, 255 to 731 days). The malignancies in these patients were as follows: breast (n = 132), lung (n = 119), stomach (n = 35), lower gastrointestinal tract (n = 106), pancreas (n = 46), kidney (n = 22), and prostate (n = 101) cancers; high-grade glioma (n = 102); malignant lymphoma (n = 94); multiple myeloma (n = 17); and other tumor types (n = 47). The study end point was occurrence of objectively confirmed symptomatic or fatal VTE. Results VTE occurred in 62 patients (7.6%). The cutoff level for elevated D-dimer and elevated F 1 + 2 was set at the 75th percentile of the total study population. In multivariable analysis that included elevated D-dimer, elevated F 1 + 2, age, sex, surgery, chemotherapy, and radiotherapy, the hazard ratios (HRs) of VTE in patients with elevated D-dimer (HR, 1.8; 95% CI, 1.0 to 3.2; P = .048) and elevated F 1 + 2 (HR, 2.0; 95% CI, 1.2 to 3.6; P = .015) were statistically significantly increased. The cumulative probability of developing VTE after 6 months was highest in patients with both elevated D-dimer and elevated F 1 + 2 (15.2%) compared with patients with nonelevated D-dimer and nonelevated F 1 + 2 (5.0%; P < .001). Conclusion High D-dimer and F 1 + 2 levels independently predict occurrence of VTE in patients with cancer.

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