Methylation profile of colon cancer genes in colorectal precursor lesions and tumor tissue: perspectives for screening

Abstract Carcinoembryonic antigen and activities of glucosephosphate isomerase (EC 5.3.1.9), γ-glutamyltransferase (EC 2.3.2.2), and lactate dehydrogenase (EC 1.1.1.27) were measured in aqueous extracts of fetal, normal adult, and malignant human colon tissues. Fetal colon, as well as primary and metastatic colon tumor tissue, showed higher activities of these analytes than did normal adult human colon. Liver metastases of colon cancer gave the highest values, normal adult human colon the lowest. Statistically, these differences were more striking in the case of carcinoembryonic antigen and glucosephosphate isomerase than for γ-glutamyltransferase or lactate dehydrogenase. In contrast to the other markers, γ-glutamyltransferase activity was lower in fetal organs than in normal adult colon and colon tumors. These results are consistent with earlier observations that activities of these markers are significantly increased in the blood of patients with metastatic colon cancer.

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Defining the polyposis/colorectal cancer phenotype associated with the Ashkenazi GREM1 duplication: counselling and management recommendations

Genetics Research ◽

10.1017/s0016672316000021 ◽

2016 ◽

Vol 98 ◽

Cited By ~ 8

Author(s):

JAMES ZIAI ◽

ELLEN MATLOFF ◽

JAEHYUK CHOI ◽

NINANI KOMBO ◽

MIGUEL MATERIN ◽

...

Keyword(s):

Colon Cancer ◽

Autosomal Dominant ◽

Ashkenazi Jewish ◽

Cancer Genes ◽

Jewish Family ◽

Hereditary Colon Cancer ◽

Juvenile Polyps ◽

Cancer Phenotype ◽

Management Recommendations ◽

Dominant Condition

SummaryHereditary mixed polyposis is a genetically heterogeneous, autosomal dominant condition with adenomatous, hyperplastic and juvenile polyps. We conducted a comprehensive clinical evaluation of a large Ashkenazi Jewish family with this phenotype and performed extensive genetic testing. As seen in one previous report, a 40 kb duplication upstream of GREM1 segregated with the polyposis/colon cancer phenotype in this kindred. Our study confirms the association of GREM1 with mixed polyposis and further defines the phenotype seen with this mutation. This gene should be included in the test panel for all Jewish patients with mixed polyposis and may be considered in any Ashkenazi patient with unexplained hereditary colon cancer when mutations in other hereditary colon cancer genes have been ruled out.

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Single-Cell Analysis Reveals Characterization of Infiltrating T Cells in Moderately Differentiated Colorectal Cancer

Frontiers in Immunology ◽

10.3389/fimmu.2020.620196 ◽

2021 ◽

Vol 11 ◽

Author(s):

Xi Yang ◽

Quan Qi ◽

Yuefen Pan ◽

Qing Zhou ◽

Yinhang Wu ◽

...

Keyword(s):

Colorectal Cancer ◽

Rectal Cancer ◽

Colon Cancer ◽

T Cells ◽

T Cell ◽

Single Cell ◽

Peripheral Blood ◽

Strong Correlation ◽

Tumor Tissue ◽

Cell Populations

ObjectiveThis study aimed to characterize the tumor-infiltrating T cells in moderately differentiated colorectal cancer.MethodsUsing single-cell RNA sequencing data of isolated 1632 T cells from tumor tissue and 1252 T cells from the peripheral blood of CRC patients, unsupervised clustering analysis was performed to identify functionally distinct T cell populations, followed by correlations and ligand-receptor interactions across cell types. Finally, differential analysis of the tumor-infiltrating T cells between colon cancer and rectal cancer were carried out.ResultsA total of eight distinct T cell populations were identified from tumor tissue. Tumor-Treg showed a strong correlation with Th17 cells. CD8+TRM was positively correlated with CD8+IEL. Seven distinct T cell populations were identified from peripheral blood. There was a strong correlation between CD4+TN and CD4+blood-TCM. Colon cancer and rectal cancer showed differences in the composition of tumor-infiltrating T cell populations. Tumor-infiltrating CD8+IEL cells were found in rectal cancer but not in colon cancer, while CD8+ TN cells were found in the peripheral blood of colon cancer but not in that of rectal cancer. A larger number of tumor-infiltrating CD8+ Tex (88.94%) cells were found in the colon cancer than in the rectal cancer (11.06%). The T cells of the colon and rectal cancers showed changes in gene expression pattern.ConclusionsWe characterized the T cell populations in the CRC tumor tissue and peripheral blood.

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Abstract 4386: Identification of clinically relevant colon cancer genes predictve of improved relapse free survival

10.1158/1538-7445.am2017-4386 ◽

2017 ◽

Author(s):

Marie J. Parsons

Keyword(s):

Colon Cancer ◽

Cancer Genes ◽

Relapse Free Survival ◽

Free Survival

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Effect of dairy products on initiation of precursor lesions of colon cancer in rats

Nutrition and Cancer ◽

10.1080/01635589509514400 ◽

1995 ◽

Vol 24 (2) ◽

pp. 121-132 ◽

Cited By ~ 62

Author(s):

Hasnaà Abdelali ◽

Pierrette Cassand ◽

Valérie Soussotte ◽

Michéle Daubeze ◽

Christine Bouley ◽

...

Keyword(s):

Colon Cancer ◽

Dairy Products ◽

Precursor Lesions

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Circulating tumor (ct)-DNA alterations in urothelial/bladder cancer (UC/BC): Updates on a dynamic genomic landscape.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.4534 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 4534-4534 ◽

Cited By ~ 2

Author(s):

Petros Grivas ◽

Rebecca J Nagy ◽

Gregory Russell Pond ◽

Sumati Gupta ◽

Jue Wang ◽

...

Keyword(s):

Tumor Tissue ◽

Clonal Evolution ◽

Median Number ◽

Cancer Genes ◽

Genomic Landscape ◽

Urothelial Bladder ◽

Dna Alterations ◽

New Gene ◽

Ctdna Analysis ◽

Serial Samples

4534 Background: Cell-free ctDNA may be potentially actionable, may have prognostic/predictive role and evolve after therapy. We updated our analysis of our retrospective study to shed light on UC/BC biology. Methods: Patients (pts) with UC/BC with ctDNA analysis for potentially actionable alterations using Guardant360 were identified. A 70-gene ctDNA next generation sequencing panel from a CLIA-licensed, CAP-accredited laboratory (Guardant Health, Inc.) offers complete exon sequencing for 29 cancer genes, critical exons in 39 genes and amplifications (16 genes), fusions (6 genes) and indels (3 genes) harvested from 10 mL of peripheral blood. Descriptive statistics were used. Results: There were 246 pts with 276 samples. At least 1 alteration was detected in 249 (90%) samples. Median age at time of ctDNA collection was 67 years (39-85), 78% men, median number of alterations per sample was 3.5 (1-35) most pts had MIBC. In MIBC pts, the most common alterations at the 1st ctDNA sample were in TP53 (52%), PI3KCA (18%) ARID1A (17%), FGFR2 (15%), MET & NF1 (14%), EGFR (13%), BRAF (12%), FGFR3 (11%), RAF1 (10%), BRCA1 & CCNE1 (9%). In MIBC pts, the most common genes with increased copy number were RAF1 & CCNE1 (8%), ERBB2 & PI3KCA (7%), EGFR, BRAF, FGFR1, MYC (each 5%), MET (4%), KRAS (3%). Most common altered pathways included TP53 signaling (56%), RAS/RAF/MEK/ERK (51%), RTK (48%), cell cycle (38%), FGFR family (34%), DNA damage response (25%), PI3KCA/AKT/mTOR (23%) and chromatin remodeling (17%). Interestingly, FGFR3 and RAS alterations were mutually exclusive in most cases, but each may co-occur with TP53alterations. 54 serial ctDNA samples from 24 pts (18 pts with 2 samples; 6 pts with 3 samples) revealed persistent, lost and new gene alterations. Conclusions: ctDNA was detected in 90% of pts and alterations were similar to those previously seen in UC tumor tissue. Tumor heterogeneity, interim therapy, genomic instability and clonal evolution can explain differences in serial samples. Correlation assessment with prior therapies and outcomes is being pursued to inform trial designs. Prospective validation, assessment of ctDNA concordance with tumor tissue DNA, and evaluation of clinical utility is warranted.

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Circulating tumor DNA analysis using targeted sequencing of 508 clinically actionable genes in patients with high grade serous ovarian cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.5582 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 5582-5582

Author(s):

Anniina Färkkilä ◽

Liina Salminen ◽

Kaisa Huhtinen ◽

Sakari Hietanen ◽

Seija Elisa Grenman ◽

...

Keyword(s):

Ovarian Cancer ◽

Tumor Tissue ◽

Genetic Alterations ◽

Gene Panel ◽

Targeted Sequencing ◽

Primary Therapy ◽

High Grade ◽

Serous Ovarian Cancer ◽

Cancer Genes ◽

Treatment Toxicity

5582 Background: The prediction of tumor chemoresponse and treatment toxicity is crucial for optimal patient care in high grade serous ovarian cancer (HGSC). We employed a targeted sequencing panel of 508 clinically annotated cancer genes to screen for actionable genetic variants in tumor tissue and ctDNA of patients with advanced HGSC. Methods: Tumor tissue, and serial plasma samples at diagnosis and during primary therapy were obtained from five patients with FIGO Stage IIIc HGSC. All patients were surgically debulked and received standard carboplatin and paclitaxel chemotherapy. DNA isolated from tumor tissue and plasma was analyzed for genetic alterations by targeted deep-sequencing of 508 previously annotated cancer genes. Somatic variants were systematically reported for alterations related to drug sensitivity and treatment toxicity, and analyzed with respect to clinical parameters and primary therapy outcomes. Results: In tumor tissues, and the corresponding pre-treatment ctDNA, oncogenic mutations were detected at a median of 13.0 and 1.6 allelic frequencies, respectively. The mutation frequency was higher, and also more unique mutations were detected in ctDNA of patients presenting with high tumor spread. Interestingly, a de-novo ctDNA MAPK1 mutation was detected in a sample taken during chemotherapy with partial response, while, no new mutations emerged in a patient with complete response. Analysis of the pretreatment plasma ctDNA revealed profiles of low and high drug sensitivities consistent with the clinical course of the patients. In two patients, increased risk profiles for treatment toxicities were identified via e.g. GSTP1. Consistently, these two patients were forced to discontinue standard therapy. Conclusions: Panel-based targeted sequencing of ctDNA identified potentially actionable mutations, and reflected tumor heterogeneity of HGSC. Further, the ctDNA gene panel annotations showed concordance with the chemoresponse- and treatment toxicity profiles, suggesting that ctDNA gene panel maybe a feasible approach to individualize treatment of HGSC patients.

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VEGF-and EGF-mediated cooperation of eosinophilic granulocytes and tumor cells in gastric and colon cancer

Bulletin of Siberian Medicine ◽

10.20538/1682-0363-2019-1-211-219 ◽

2019 ◽

Vol 18 (1) ◽

pp. 211-219

Author(s):

Yu. V. Kolobovnikova ◽

K. I. Yankovich ◽

E. V. Romanova ◽

A. I. Dmitrieva ◽

O. I. Urazova ◽

...

Keyword(s):

Gastric Cancer ◽

Colon Cancer ◽

Growth Factor ◽

Tumor Cells ◽

Tumor Tissue ◽

Malignant Tumors ◽

Tissue Eosinophilia ◽

Eosinophilic Granulocytes ◽

Blood Eosinophils

Aim of the research – to analyze secretion of vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) by blood eosinophilic granulocytes in vitro, together with an expression of VEGFR and EGFR in tumor tissue in gastric and colon cancer in association with tissue eosinophilia.Materials and methods. A total of 52 patients with gastric cancer and 50 patients with colon cancer were examined. The material of the research included supernatants of eosinophil cultures and samples of malignant tumors tissues of the stomach and colon. Enzyme-linked immunosorbent assay was used to determine the contents of VEGF and EGF in the eosinophil culture supernatants in vitro. The expression of VEGFR and EGFR in tumor tissue was evaluated by immunohistochemistry. The results were analyzed by statistical methods.Results. An increase in basal and r-IL-5-induced secretion of VEGF by eosinophilic granulocytes of blood in vitro was found in patients with gastric cancer accompanied by tissue eosinophilia. The concentration of EGF in the culture of blood eosinophils in vitro with the addition of r-IL-5 increased in patients with eosinophilic infiltration of tumor tissue, regardless of the localization of the pathological process,both in patients with gastric cancer and colon cancer. Eosinophilic infiltration of the tumor tissue in gastric cancer and colon cancer was combined with hypo-expression of EGFR by tumor cells; VEGFR receptor expression was not dependent on the presence of eosinophilic granulocytes in the tissue of tumors.Conclusion. Hypersecretion of vascular endothelial growth factor VEGF and epidermal growth factor EGF (upon stimulation with r-IL-5) by blood eosinophils in vitro in patients with gastric and colon cancer with tissue eosinophilia indicates an increase in the activity of these cells. Deficiency of expression of VEGF and EGFR receptors in tumor tissue causes violation of cooperative interaction of eosinophilic granulocytes and tumor cells in malignant tumors of the stomach and large intestine.

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