scholarly journals Characterization of genomic alterations in Chinese colorectal cancer patients

2020 ◽  
Vol 51 (1) ◽  
pp. 120-129
Author(s):  
Wei Huang ◽  
Hui Li ◽  
Xiaoliang Shi ◽  
Minglin Lin ◽  
Cun Liao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Genomic Alteration ◽  
Molecular Characteristics ◽  
Tumor Differentiation ◽  
Cancer Genes ◽  
Exact Test ◽  
Mutational Burden ◽  
Tumor Mutational Burden ◽  
Colorectal Cancer Patients

Abstract Objective Colorectal cancer is one of the most prevalent types of cancer worldwide. Right-sided and left-sided colorectal cancer (RCC and LCC) patients respond differently to treatment. We aimed to identify the different mutational profile between RCC and LCC and provided evidence for future precision therapy. Methods A total of 630 Chinese colorectal cancer patients, including 467 (74.1%) LCC and 163 (25.9%) RCC, were enrolled in this cohort. Both formalin-fixed paraffin-embedded tumor tissues and matching blood samples were collected and deep sequenced targeting 450 cancer genes for genomic alteration analysis. Tumor mutational burden was measured by an algorithm developed in-house. Correlation analysis was performed by Fisher’s exact test. Results The most common mutated genes were TP53 (77.0%), APC (71.7%), KRAS (50.0%), SMAD4 (19.8%), PIK3CA (18.3%), FBXW7 (17.5%), TCF7L2 (12.5%), SOX9 (11.3%), LRP1B (10.8%), ARID1A (10.3%) and FAT4 (10.3%). The mutation frequencies of TP53 and APC in LCC were significantly higher than that of RCC, while the mutation frequency of PIK3CA was lower than that of RCC. Six gene fusions were specifically detected in RCC patients. Colorectal cancer sites were associated with gender (P = 4.15 × 10−5) and tumor differentiation (P = 0.059). In LCC, the gender-associated genes were FAT4, EP300, FAT1, LRP1, ARID1B, AR, FYN and TAF1, while in RCC, they were ARID1A, SMARCA4, LRP1 and GRIN2A. The mutations of 18 genes were associated with tumor differentiation (8 for LCC and 10 for RCC). High tumor mutational burden was more common in RCC. Our results implied more potential targeted drug therapy opportunities for RCC. Conclusion We describe the different molecular characteristics of LCC and RCC. Our result supported a better prognosis of RCC than LCC in Chinese colorectal cancer patients.

scholarly journals Characteristics of genomic alterations in Chinese cholangiocarcinoma patients

2020 ◽  
Vol 50 (10) ◽  
pp. 1117-1125
Author(s):  
Guoping Jiang ◽  
Wu Zhang ◽  
Ting Wang ◽  
Songming Ding ◽  
Xiaoliang Shi ◽  
...  
Keyword(s):  
Genomic Alteration ◽  
Molecular Evidence ◽  
Cancer Genes ◽  
Primary Malignancy ◽  
Exact Test ◽  
Mutational Burden ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Tumor Mutational Burden ◽  
Formalin Fixed

Abstract Objective Cholangiocarcinoma (CCA) is a primary malignancy, which is often diagnosed as advanced and inoperable due to the lack of effective biomarkers and poor sensitivity of clinical diagnosis. Here, we aimed to identify the genomic profile of CCA and provided molecular evidence for further biomarker development. Methods The formalin-fixed paraffin-embedded and matching blood samples were sequenced by deep sequencing targeting 450 cancer genes and genomic alteration analysis was performed. Tumor mutational burden (TMB) was measured by an algorithm developed in-house. Correlation analysis was performed by Fisher’s exact test. Results The most commonly altered genes in this cohort were TP53 (41.27%, 26/63), KRAS (31.75%, 20/63), ARID1A and IDH1 (15.87%, 10/63, for both), SMAD4 (14.29%, 9/63), FGFR2 and BAP1 (12.70%, 8/63, for both), and CDKN2A (11.11%, 7/63). BAP1 mutations were significantly correlated with the CCA subtype. LRP2 mutations were significantly associated with the younger intrahepatic CCA (iCCA) patients, while BAP1 was associated with iCCA patients aged 55–65 years old. BAP1 and LRP2 mutations were associated with TMB. Conclusions Most Chinese CCA patients were 50–70 years old. BAP1 and LRP2 mutations were associated with the age of iCCA patients.

scholarly journals BSM1 Polymorphism Association in Vitamin D Receptor Genes with the Occurrence of Colorectal Cancer in Palembang, Indonesia

2020 ◽  
Vol 55 (6) ◽  
Author(s):  
M. Alsen Arlan ◽  
Sarup Singh ◽  
Efman E.U. Manawan ◽  
M. Hafidh Komar ◽  
Irsan Saleh
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Vitamin D ◽  
Cancer Patients ◽  
Vitamin D Receptor ◽  
Protective Factor ◽  
Control Group ◽  
Exact Test ◽  
Cancer Occurrence ◽  
Colorectal Cancer Patients

This paper analyzed the association between Bsm1 polymorphism in vitamin D receptor genes with colorectal cancer patients in Palembang, Indonesia. This case control study was conducted from June 2019 to December 2019. The genotype was analyzed using polymerase chain reaction-restriction fragment length polymorphism with the Bsm1 restriction enzyme. Findings showed the distribution of BB-Bb-bb genotype among colorectal cancer patients was 18.6%:26.7%:4.7%, whereas the distribution in a control group was 0%:43%:7%. The distribution of B and b alleles in colorectal cancer patients was 32%:18% compared to the control group’s distribution of 21.5%:28.5%. A statistical analysis of Fisher's exact test was conducted to examine the association of polymorphism with colorectal cancer occurrence. Findings demonstrated that there is a significant association was found between Bsm1 polymorphism of vitamin D receptor genes and colorectal cancer occurrences among patients in Palembang, Indonesia. Detailed analysis revealed that rs1544410 in the genotype BB might be a causal factor for colon cancer occurrence. Allele B on the other hand was reported to be the protective factor against colon cancer.

Two immunoglobulin G fragment C receptor polymorphisms associated with clinical outcome of EGFR-expressing metastatic colorectal cancer patients treated with single agent cetuximab

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3028-3028 ◽  
Author(s):  
W. Zhang ◽  
M. Gordon ◽  
A. M. Schultheis ◽  
F. Nagashima ◽  
M. Azuma ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Monoclonal Antibody ◽  
Clinical Outcome ◽  
Metastatic Colorectal Cancer ◽  
Cancer Patients ◽  
Immunoglobulin G ◽  
Tumor Response ◽  
Single Agent ◽  
Exact Test ◽  
Colorectal Cancer Patients

3028 Background: Cetuximab is a chimeric immunoglobulin G1 anti-EGFR monoclonal antibody with efficacy in metastatic colorectal cancer patients refractory to irinotican chemotherapy. Recent studies show that Antibody-dependent cellular cytotoxicity (ADCC) mediated through Fc receptors plays an important role in the antitumor effect of IgG1 antibody. There are three classes of FcγRs involved in the regulation of ADCC. FcγRIIa(CD32) and FcγRIIIa(CD16) activates and FcγRIIb inhibits activation. Clinical studies show FcγRIIIa 158 V/F polymorphism was associated with tumor response and progression-free survival in the follicular lymphoma patients treated with rituximab as first line treatment. Also, a H/R polymorphism at position 131 of FcγRIIa has been found to affects its affinity to human IgG and independently predict response to Rituximab. Since Cetuximab and Rituximab belong to the same chimeric IgG1 monoclonal antibody, we test hypothesis whether these two FcγR polymorphisms associated with clinical outcome in colorectal cancer patients treated with single agent Cetuximab. Methods: we tested both FcγRIIIa 158 V/F and FcγRIIa 131 H/R gene polymorphisms using PCR-RFLP method in genomic DNA extracted from peripheral blood from 39 EGFR-expressing metastatic colorectal cancer patients enrolled in a phase II single agent Cetuximab treatment clinical trial (IMCL-0144). Results: We found patients with FcγRIIa 131 HH or HR genotype show better time to progression and overall survival compare to patients with R/R genotype (p=0.037, p=0.22, respectively, log-rank test). Also, there is trend significance in tumor response when we compare patients with RR genotype and patients with HH or HR genotype (p=0.08, fisher’s exact test). FcγRIIIa 158 V/F also show trend significance in tumor response (p=0.067, fisher’s exact test). Conclusions: These data suggest Two Immunoglobulin G Fragment C Receptor polymorphismsFcγRIIIa158V/F andFcγRIIa 131 H/R may be potential molecular markers for clinical outcome of refractory metastatic colorectal caner patients treated with single agent EGFR inhibitor Cetuximab. Prospective studies are needed to confirm these preliminary findings. [Table: see text]

Tumor mutational burden of microsatellite stable metastatic colorectal tumors by patient factors and KRAS, BRAF, and PIK3CA mutation status.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 627-627 ◽  
Author(s):  
Jun Gong ◽  
Marvin Sy ◽  
Marwan Fakih
Keyword(s):  
Colorectal Cancer ◽  
Primary Tumor ◽  
Pik3ca Mutation ◽  
Older Individuals ◽  
Colorectal Tumors ◽  
Patient Factors ◽  
Pik3ca Mutations ◽  
Mutational Burden ◽  
Tumor Mutational Burden ◽  
Colorectal Cancer Patients

627 Background: Microsatellite instability (MSI) can predict response to pembrolizumab in metastatic colorectal cancer (mCRC). Benefit to PD-1 blockade is limited in microsatellite stable (MSS) mCRC yet MSS tumors represent >95% of all mCRC cases. Evidence suggests that high mutational load remains an important predictor of benefit to checkpoint inhibition across several tumors. We aimed to explore associations between tumor mutational burden (TMB) and various patient factors and mutations of interest to identify features of patients (pts) with MSS mCRC of potential significance to prognosis and PD-1 targeting. Methods: We conducted a retrospective study based on next-generation sequencing (NGS) of MSS metastatic colorectal tumors at our single institution using FoundationOne. TMB was categorized as high ≥ 20 mutations/megabase (Mb), intermediate 6-19 mutations/Mb, and low ≤ 5 mutations/Mb. TMB frequencies were analyzed according to age (≤50, >50, >65, and >70 years old), gender, race, location of primary tumor, and KRAS, BRAF, and PIK3CA mutations. Results: Among 194 MSS tumors with available TMB data, frequencies of tumors with intermediate TMB were significantly different in pts ≤50 years (24.6%, n=69) than in pts >65 (48.9%, n=47, Fisher’s exact (two-tailed) p=0.0096) and >70 (53.1%, n=32, p=0.0067). Frequencies of tumors with low TMB were significantly different in pts ≤50 years (75.4%, n=69) than in pts >65 (46.8%, n=47, p=0.0029) and >70 (43.8%, n=32, p=0.0032). Frequencies of high TMB tumors by age were 0% (≤50 years), 1.6% (>50), 4.3% (>65), and 3.1% (>70) and did not reach significance. Frequencies of high, intermediate, or low TMB tumors were not significantly different based on gender, race, and location of primary tumor. Frequencies of KRAS, BRAF, and PIK3CA mutations were similar across all TMB categories (p=0.7995, 0.8774, and 0.053, respectively). Conclusions: Older individuals with mCRC are less likely to have a low mutation burden by FoundationOne assay. Further validation of these findings in larger cohorts may indicate a potential higher likelihood for elderly colorectal cancer patients to benefit from immune-based strategies.

Correlation of tumor mutational burden (TMB) with molecular profiling and clinical characteristics in patients with bladder cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17025-e17025
Author(s):  
Divya Natesan ◽  
Henry Martell ◽  
Patrick Devine ◽  
Bradley A. Stohr ◽  
James P. Grenert ◽  
...  
Keyword(s):  
Predictive Biomarkers ◽  
Cancer Genes ◽  
Clinicopathologic Characteristics ◽  
Exact Test ◽  
Mutational Burden ◽  
Target Dna ◽  
Tumor Mutational Burden ◽  
The Common ◽  
Next Generation Sequencing Ngs ◽  
Fgfr3 Mutations

e17025 Background: Bladder cancers (BC) are frequently highly mutated. Next generation sequencing (NGS) can both shed light on mutational burden and the specific alterations that provide insights into the underlying biology of individual tumors. Methods: We retrospectively reviewed BC cases assessed with UCSF500, an institutional NGS assay that uses hybrid capture enrichment of target DNA to interrogate approximately 500 frequently mutated cancer genes. Hypermutated tumors were defined as having TMB > 10 mutations/Mb. Fisher’s exact test was used to compare patients (pts) with hypermutated (HM) and non-hypermutated (NHM) tumors. Results: From 2015 to 2019, 74 pts with BC underwent UCSF500 testing; 48 pts were evaluable for TMB, of which 19 pts (40%) had HM tumors. 17/19 pts were evaluable for mutational signatures; all 17 had APOBEC signatures. Signatures were not assessed in NHM tumors due to low TMB. Clinicopathologic characteristics and most common alterations in the two groups are listed in the table. More HM pts had responses to immunotherapy (IO) treatment (86% vs 40%, p = 0.13). Conclusions: In this single-institution BC cohort, HM tumors were common and APOBEC mutational signature was the common underlying biology in HM tumors. There were relevant differences in common alterations between HM and NHM tumors, including more FGFR3 mutations in NHM tumors. HM status and APOBEC signature were suggested as relevant predictive biomarkers of response to IO, which should be investigated further in larger BC cohorts. [Table: see text]

Associations of daily partner responses with fatigue interference and relationship satisfaction in colorectal cancer patients.

2018 ◽  
Vol 37 (11) ◽  
pp. 1015-1024
Author(s):  
Fabiola Müller ◽  
Marrit A. Tuinman ◽  
Ellen Stephenson ◽  
Ans Smink ◽  
Anita DeLongis ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Relationship Satisfaction ◽  
Cancer Patients ◽  
Colorectal Cancer Patients
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