The landscape of gene fusions and the correlation with immunotherapy biomarkers in Chinese patients with advanced solid tumor.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15039-e15039
Author(s):  
Wenshuai Liu ◽  
Yifan Zhou ◽  
Bei Zhang ◽  
Yuezong Bai ◽  
Yueqi Wang
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Solid Tumor ◽  
Chinese Patients ◽  
Fisher Exact Test ◽  
Gene Fusions ◽  
Advanced Solid Tumor ◽  
Tumor Patients ◽  
Potential Biomarker ◽  
Colorectal Cancer Patients

e15039 Background: Due to the U.S. Food and Drug Administration approval of larotrectinib, a tumor or tissue-agnostic cancer treatment, gene fusions and fusion-driven cancer were identified as indications. Exploration of the gene fusions might be essential in both target therapy and immunotherapy in advanced solid tumor. However, the landscape of gene fusions in Chinese solid tumor patients is poorly reported. Methods: Tissue samples were obtained from 7514 Chinese patients with advanced solid tumor. Genomic alterations were identified via the next generation sequencing (NGS) with a validated commercial 381-cancer-gene panel (panel size over 0.5 MB), including 100 MSI loci. TMB was calculated according to NGS results. Statistical analysis was performed by Fisher exact test using R 3.6.1. Results: There were 162 pathologic or very like pathologic gene fusions observed in 249 (3.31%) patients, covering 30 cancer types. Top frequent fusion genes were ALK (93), RET (32), FGFR2 (26), FGFR3 (13), ROS1 (10), TMPRSS2 (10) and NTRK1 (9). Their main partner genes were EML4 (66/ 93), KIF5B (15/32), BICC1 (5/26), TACC3 (13/13), CD47 (3/10), ERG (9/10) and TPM3 (5/9), respectively. Mostly, only one fusion was detected in one patient. Three patients harbored 3 gene fusions and 35 patients harbored 2 gene fusions, among which 21 patients were observed harboring both fusion and its reciprocal fusion. In the group of patients harboring gene fusions, the prevalence of MSI-H was 4.0% (10/ 249). Especially, the prevalence was significant high (41.2%, 7/ 17) in colorectal cancer patients (P < 0.001). In MSI-H colorectal cancer patients, 4 carried NTRK1 fusions, 2 RET fusions and 1 ALK fusion. And all of them had high tumor mutation burden (TMB). As another immunotherapy response predictor, TMB was low in most solid tumor patients in this study, except for the patients harboring gene fusions involving NTRK1, NTRK2 or STK11, whose TMB-H proportion were 67%, 50% and 33%, respectively. Conclusions: Gene fusions might be associated with MSI-H. In colorectal cancer patients, gene fusions involved either NTRK1 or NTRK2 might be associated with TMB-H, which revealed a potential biomarker for both target and immunotherapy.

Circulating cell-free DNA in plasma of colorectal cancer patients - A potential biomarker for tumor burden

2017 ◽  
Vol 26 (4) ◽  
pp. 395-401 ◽  
Author(s):  
Jagdeep Singh Bhangu ◽  
Hossein Taghizadeh ◽  
Tamara Braunschmid ◽  
Thomas Bachleitner-Hofmann ◽  
Christine Mannhalter
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Tumor Burden ◽  
Cell Free Dna ◽  
Free Dna ◽  
Potential Biomarker ◽  
Colorectal Cancer Patients ◽  
Circulating Cell Free Dna

scholarly journals Reduced Plasma Levels of Very-Long-Chain Dicarboxylic Acid 28:4 in Italian and Brazilian Colorectal Cancer Patient Cohorts

Metabolites ◽  
2018 ◽  
Vol 8 (4) ◽  
pp. 91 ◽  
Author(s):  
Paul Wood ◽  
Michelle Donohue ◽  
John Cebak ◽  
Taylor Beckmann ◽  
Márcia Messias ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dicarboxylic Acid ◽  
Cancer Patients ◽  
Plasma Levels ◽  
High Resolution Mass Spectrometry ◽  
Sporadic Colorectal Cancer ◽  
Inherited Susceptibility ◽  
Potential Biomarker ◽  
Colorectal Cancer Patients ◽  
Long Chain

Background: There are currently no blood-based biomarkers for early diagnosis of colorectal cancer. Previous research has suggested that very-long-chain dicarboxylic acid (VLCDCA) 28:4 might be such a biomarker. Methods: Using high-resolution mass spectrometry, we analyzed VLCDCA 28:4 in the plasma of colorectal cancer patients in Italian [n = 62] and Brazilian [n = 52] cohorts. Additionally, we investigated individuals diagnosed with familial adenomatous polyposis (FAP; n = 27), one of the most important clinical forms of inherited susceptibility to colorectal cancer. Results: Decrements in plasma levels of VLCDCA 28:4 were monitored in colorectal cancer patients. These decreases were independent of the stage of tumor development and the individual’s age. However, no decrements in VLCDCA 28:4 were monitored in FAP patients. Conclusions: The plasma levels of VLCDCA 28:4 represent a potential biomarker of sporadic colorectal cancer. In addition, it is possible that resupply of this anti-inflammatory lipid may represent a new therapeutic strategy for CRC and inflammatory disorders.

Oncogenic FGFR3 gene fusions in solid tumors among Chinese cancer patients.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15072-e15072
Author(s):  
Libin Xu ◽  
Ming Liu ◽  
Jingxian Duan ◽  
Tao Wang
Keyword(s):  
Cancer Patients ◽  
Solid Tumors ◽  
Solid Tumor ◽  
Coiled Coil ◽  
Genetic Alterations ◽  
Chinese Patients ◽  
Driver Mutations ◽  
Gene Fusions ◽  
Fgfr3 Gene ◽  
Tumor Types

e15072 Background: Oncogenic FGFR3 (fibroblast growth factor receptor 3) gene fusions have been identified as driver mutations that lead to the activation of FGFR3 in many solid tumor types and serve as a novel therapeutic target for FGFR inhibitors in clinical development. TACC3 (transforming acid coiled coil 3) is the most common partner of these FGFR3 fusions. Methods: The study enrolled over ten thousand cases of Chinese patients with different types of solid tumors. We performed targeted sequencing assay with our 605 gene panel that covered all the exon and intron regions of the FGFR3 gene, so that we could identify nearly all the FGFR3 translocation events. Results: The prevalence and form of FGFR3 fusions in different tumor types were shown in Table. We identified seven patients harboring FGFR3 fusion events, with six cases of FGFR3-TACC3 and one case of FGFR3-UBE2K. In the seven patients, three of them were also harbored concomitant TP53 gene mutations, and six of them were microsatellite stability (MSS), and one was microsatellite instability-low (MSI-L). Conclusions: FGFR3 gene rearrangements were identified in different solid tumor types in our study, and they were relatively rare compared to other novel mutations. However, clinical testing for the identification of FGFR3 fusions should be prioritized in bladder cancer patients. Consistent with other studies, the most common FGFR3 fusion form was FGFR3-TACC3. Co-occurring genetic alterations in FGFR3 gene fusions cases were also common. From our limited number of cases, most of FGFR3 gene fusions patients were MSS.[Table: see text]

scholarly journals Prevalence and coexistence of KRAS, BRAF, PIK3CA, NRAS, TP53, and APC mutations in Indian colorectal cancer patients: Next-generation sequencing–based cohort study

Tumor Biology ◽  
2017 ◽  
Vol 39 (2) ◽  
pp. 101042831769226 ◽  
Author(s):  
Mayank Jauhri ◽  
Akanksha Bhatnagar ◽  
Satish Gupta ◽  
Manasa BP ◽  
Sachin Minhas ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Next Generation Sequencing ◽  
Cancer Patients ◽  
Gene Mutations ◽  
Next Generation ◽  
Kras Mutations ◽  
Pik3ca Mutations ◽  
Potential Biomarker ◽  
Colorectal Cancer Patients ◽  
Generation Sequencing

Colorectal cancer incidences are on a rise in India. In this study, we have analyzed the mutation frequencies of six potential biomarkers, their coexistence, association with clinicopathological characteristics, and tumor location in Indian colorectal cancer patients. Next-generation sequencing was performed to identify mutations in the six potential biomarker genes using formalin-fixed paraffin-embedded tissue blocks of 112 colorectal cancer patients. The mutation frequency observed in KRAS, BRAF, PIK3CA, NRAS, TP53, and APC was 35.7%, 7.1%, 16.1%, 6.3%, 39.3%, and 29.5%, respectively. The significant associations of mutations were KRAS with age less than 60 years (p = 0.041), PIK3CA with males (p = 0.032), tumor stage I–II (p = 0.013), lack of metastasis in lymph nodes (p = 0.040), NRAS with rectum (p = 0.002), and APC with T2 stage of tumor growth (p = 0.013). No single patient harbored mutations in these six genes or any five genes simultaneously. Significance was noted in coexistence of KRAS with APC (p = 0.024) and mutual exclusion of KRAS with BRAF (p = 0.029). PIK3CA exon 9 was observed to be more frequently associated with KRAS mutations than PIK3CA exon 20 (p = 0.072). NRAS mutations were mutually exclusive with BRAF and PIK3CA mutations. As per our knowledge, this is the first next-generation sequencing–based biomarker study in Indian colorectal cancer patients. Frequent coexistence of gene mutations in pairs and triplets suggests that synergistic effect of overlapping mutations might further trigger the disease. In addition, infrequent coexistence of multiple gene mutations hints toward different signaling pathways for colorectal cancer tumorigenesis.

scholarly journals Clinical characteristics and prognostic value of the KRAS mutation in Chinese colorectal cancer patients

2021 ◽  
pp. 172460082110171
Author(s):  
Ye Yuan ◽  
Yingting Liu ◽  
Ye Wu ◽  
Junling Zhang ◽  
Chunti Shen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
High Frequency ◽  
Kras Mutation ◽  
Chinese Patients ◽  
Wild Type ◽  
Kras Mutations ◽  
Exon 2 ◽  
Colorectal Cancer Patients

Background: The KRAS mutations are high-frequency somatic mutations found in colorectal cancer patients from Western and Asian countries however, with the exception of exon 2 of KRAS, other prevalence and prognostic values have not been adequately assessed in Asian patients. The aim of this study was to determine the mutation frequencies of whole exon mutations of KRAS in Chinese colorectal cancer patients and to investigate their impact on prognosis. Methods: A total of 7189 tumor tissue samples (iCohort) were subjected to next-generation sequencing for detection of KRAS mutations. All pathologic or likely pathologic mutations of KRAS were considered. In addition, clinical features and prognostic dates were collected from 145 patients at The Third Affiliated Hospital of Soochow University, China (sCohort) and used droplet digital™ polymerase chain reaction to detect KRAS mutations. Results: In the iCohort, 2706 patients (37.6%) were confirmed harboring KRAS mutations. The most frequent of these mutations were G12D (32.19%), G12V (17.96%), and G13D (17.59%). In the sCohort, 51 colorectal cancer patients (35.17%) had KRAS mutations, among which KRAS G12D (64.71%), G13D (29.41%), and G14D (3.92%) were high-frequency. The KRAS mutations were associated with shorter median overall survival than wild-type tumors (69 vs. 55 months; HR 1.80; 95% Cl 1.22, 2.64; P=0.0003). In the Cox multivariate analysis, age (HR 1.562; 95% Cl 1.10, 2.22; P=0.013), tumor differentiation (HR 0.417; 95% Cl 0.19, 0.90; P=0.026), and KRAS mutation (HR 1.897; 95% Cl 0.19, 0.90; P=0.001) remained independent predictors of shorter overall survival. Among the common KRAS mutations, G12D was significantly associated with shorter overall survival (HR 2.17; 95% Cl 1.31, 3.58; P < 0.0001) compared with KRAS wild-type patients. Conclusions: Our findings indicate that KRAS genes are frequently mutated, and over 30% harbored the KRAS G12D mutation subtype. We found that the KRAS G12D mutation is associated with inferior survival and is a biomarker of poor prognosis in Chinese patients. Our data emphasize the importance of molecular features in colorectal cancer patients, which could potentially be improved by G12D-specific related inhibitors.

Serum chitinase activity to predict survival and metastasis of colorectal cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15105-e15105 ◽  
Author(s):  
Zhangfa Song
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastases ◽  
Cancer Patients ◽  
Peripheral Blood ◽  
Colorectal Cancer Patient ◽  
Chitinase Activity ◽  
Synchronous Liver Metastases ◽  
Potential Biomarker ◽  
Cox Analysis ◽  
Colorectal Cancer Patients

e15105 Background: In this study we evaluated the role of the chitinase activity (one of the biomarkers) in predicting the liver metastases of colorectal cancer in blood. Methods: The level of chitinase activity were examined in 400 colorectal cancer patients, including 53 synchronous liver metastases in peripheral blood 0.347 colorectal cancer patients peripheral blood was measured before resection of the cancer. The clinical parameters were collected, and the patient were prospectively followed up. Results: The chitinase activity was significantly over-expressed in synchronous liver metastases than colorectal cancer who has no metastases. During the follow up in 347 colorectal cancer patient, higher expression of chitinase activity, higher risk of liver metastases, bothunivariate cox analysis (HR6.0) and multivariate Cox analysis (HR 5.3) show chitinase has high value of predictive the liver metastases after resection of the primary colorectal cancer. Kaplan-Meier analysis shows the chitinase activity has significant correlation to survival in colorectal cancer patients. Moreover, the in vitro study shows the chitinase play important role in cell migration. The metastasis ratio between two groups in non-synchronic colorectal metastasis patients. Conclusions: This study provide experimental evidence that chitinase activity has the potential biomarker for predictive the liver metastases in colorectal cancer. [Table: see text]

CX1003 quantification by ultra-performance LC–MS/MS in human plasma and its application to a pharmacokinetic study in solid tumor patients

Bioanalysis ◽  
2019 ◽  
Vol 11 (16) ◽  
pp. 1483-1493
Author(s):  
Yu Li ◽  
Qian Zhao ◽  
Pei Hu ◽  
Ji Jiang
Keyword(s):  
Cancer Patients ◽  
Human Plasma ◽  
Solid Tumors ◽  
Pharmacokinetic Study ◽  
Solid Tumor ◽  
Receptor Tyrosine Kinase ◽  
Kinase Inhibitor ◽  
Chinese Patients ◽  
Good Sensitivity ◽  
Tumor Patients

Aim: CX1003 is a novel multitargeted receptor tyrosine kinase inhibitor targeting cancer patients with relapsed or metastatic malignant solid tumors. The study aimed to develop a robust and rapid assay approach to quantify CX1003 in human plasma. Methodology & results: Samples of plasma were purified by SPE where the diluted eluates were then separated by a Waters Acquity CSH C18 column and thereafter detected using positive electrospray ionization via an ultra performance LC–MS/MS. Conclusion: The method to quantify CX1003 in human plasma was first exploited and validated with good sensitivity and specificity, and successfully fulfilled the requirement of the first-in-human clinical pharmacokinetic study of CX1003 in Chinese patients with relapsed or metastatic malignant solid tumors.

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