scholarly journals Genomic evolution during locoregional recurrence in colorectal cancer determined by whole-exome sequencing

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Xiaoliang Lan ◽  
Xiaoxiao Wu ◽  
Chao Zhang ◽  
Genxia Wei ◽  
Bingbing Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Locoregional Recurrence ◽  
Genomic Evolution ◽  
Whole Exome

scholarly journals Whole exome sequencing analysis of urine trans-renal tumour DNA in metastatic colorectal cancer patients

ESMO Open ◽  
2019 ◽  
Vol 4 (6) ◽  
pp. e000572
Author(s):  
Giovanni Crisafulli ◽  
Benedetta Mussolin ◽  
Andrea Cassingena ◽  
Monica Montone ◽  
Alice Bartolini ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Molecular Weight ◽  
Metastatic Colorectal Cancer ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genetic Information ◽  
Renal Tumour ◽  
Low Molecular Weight ◽  
Sequencing Analysis ◽  
Whole Exome

BackgroundThe analysis of circulating free tumour DNA (ctDNA) in blood, commonly referred as liquid biopsy, is being used to characterise patients with solid cancers. Tumour-specific genetic variants can also be present in DNA isolated from other body fluids, such as urine. Unlike blood, urine sampling is non-invasive, can be self-performed, and allows recurrent longitudinal monitoring. The features of tumour DNA that clears from the glomerular filtration barrier, named trans-renal tumour DNA (trtDNA), are largely unexplored.Patients and methodsSpecimens were collected from 24 patients with KRAS or BRAF mutant metastatic colorectal cancer (mCRC). Driver mutations were assessed by droplet digital PCR (ddPCR) in ctDNA from plasma and trtDNA from urine. Whole exome sequencing (WES) was performed in DNA isolated from tissue, plasma and urine.ResultsOut of the 24 CRC cases, only four had sufficient DNA to allow WES analyses in urine and plasma. We found that tumour alterations primarily reside in low molecular weight fragments (less than 112 bp). In patients whose trtDNA was more than 2.69% of the urine derived DNA, cancer-specific molecular alterations, mutational signatures and copy number profiles identified in urine DNA are comparable with those detected in plasma ctDNA.ConclusionsWith current technologies, WES analysis of trtDNA is feasible in a small fraction of mCRC patients. Tumour-related genetic information is mainly present in low molecular weight DNA fragments. Although the limited amounts of trtDNA poses analytical challenges, enrichment of low molecular weight DNAs and optimised computational tools can improve the detection of tumour-specific genetic information in urine.

scholarly journals Metastatic colorectal cancer and severe hypocalcemia following irinotecan administration in a patient with X-linked agammaglobulinemia: a case report

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Mingming Li ◽  
Wei Chen ◽  
Xiaomeng Sun ◽  
Zhipeng Wang ◽  
Xun Zou ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Therapeutic Drug Monitoring ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Drug Monitoring ◽  
Treatment Cycle ◽  
Germline Mutations ◽  
Therapeutic Drug ◽  
Immune Disorder ◽  
Whole Exome

Abstract Background X-linked agammaglobulinemia (XLA) is a primary immunodeficiency disorder caused by germline mutations in the Bruton tyrosine kinase (BTK) gene on X chromosome. These mutations disturb B-cell development, decrease immunoglobulin levels, increase susceptibility to infection or neoplasms, and increase the risk of developing colorectal cancer (CRC). For occasional cases of CRC have been reported in XLA patients, low levels of B lymphocytes and immunoglobulins induced by congenital immune disorder make them more susceptible to drug-related toxicities (DRT). Therefore, gene sequencing, therapeutic drug monitoring and any possible measurement to predict DRT should be considered before determining the course of chemotherapy for XLA patients with CRC. Case presentation In this study, we reported a 21-year-old male who developed metastatic CRC in the context of XLA. Since the whole exome sequencing and therapeutic drug monitoring did not reveal any predictive markers of DRT, we applied standard first-line chemotherapy to the patient. However, progressive disease occurred after the fifth treatment cycle. Therefore, the administration of oxaliplatin was changed to irinotecan as second-line therapy. After that, the patient firstly suffered from severe hypocalcemia and eventually died due to metastatic CRC after the eighth treatment cycle. The overall survival time was 7.5 months. Conclusions This study reported the first written record of a Chinese XLA patient with metastatic CRC and severe hypocalcemia. Whole exome sequencing and bioinformatic analysis indicated the somatic mutations in ABCA6, C6 and PAX3 genes might contribute to the early-onset and metastasis CRC. Besides, a number of germline mutations in genes related to calcium metabolism (CACNA2D4, CD36, etc.) and the administration of irinotecan were speculated to be the causes of severe hypocalcemia. We therefore suggested that in order to avoid severe DRT, clinicians should take genetic background and therapeutic drug monitoring into consideration while planning chemotherapy treatment for XLA patients with CRC.

scholarly journals Using linkage studies combined with whole‐exome sequencing to identify novel candidate genes for familial colorectal cancer

2019 ◽  
Vol 146 (6) ◽  
pp. 1568-1577 ◽  
Author(s):  
Claudio Toma ◽  
Marcos Díaz‐Gay ◽  
Sebastià Franch‐Expósito ◽  
Coral Arnau‐Collell ◽  
Bronwyn Overs ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Exome Sequencing ◽  
Candidate Genes ◽  
Whole Exome Sequencing ◽  
Linkage Studies ◽  
Familial Colorectal Cancer ◽  
Whole Exome

scholarly journals Whole-exome sequencing identifies rare pathogenic variants in new predisposition genes for familial colorectal cancer

2014 ◽  
Vol 17 (2) ◽  
pp. 131-142 ◽  
Author(s):  
Clara Esteban-Jurado ◽  
◽  
Maria Vila-Casadesús ◽  
Pilar Garre ◽  
Juan José Lozano ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Familial Colorectal Cancer ◽  
Pathogenic Variants ◽  
Whole Exome ◽  
Predisposition Genes

scholarly journals Whole Exome Sequencing Identifies APCDD1 and HDAC5 Genes as Potentially Cancer Predisposing in Familial Colorectal Cancer

2021 ◽  
Author(s):  
Diamanto Skopelitou ◽  
Beiping Miao ◽  
Aayushi Srivastava ◽  
Abhishek Kumar ◽  
Magdalena Kuświk ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Promoter Activity ◽  
Luciferase Reporter ◽  
Familial Colorectal Cancer ◽  
Complex Disorders ◽  
Whole Exome ◽  
Predisposition Genes ◽  
Genetic Burden

Germline mutations in predisposition genes account for only 20% of all familial colorectal cancer (CRC) and the remaining genetic burden may be due to rare high-to-moderate-penetrance germline variants that are not explored. With the aim of identifying such potential cancer predisposing variants, we performed whole exome sequencing on three CRC cases and three unaffected members of a Polish family and identified two novel heterozygous variants; a coding variant in APC down-regulated 1 gene (APCDD1, p.R299H) and a non-coding variant in the 5’ untranslated region (UTR) of histone deacetylase 5 gene (HDAC5). Sanger sequencing confirmed the variants segregating with the disease and Taqman assays revealed 8 additional APCDD1 variants in a cohort of 1705 familial CRC patients and no further HDAC5 variants. Proliferation assays indicated an insignificant proliferative impact for the APCDD1 variant. Luciferase reporter assays using the HDAC5 variant resulted in an enhanced promoter activity. Targeting of transcription factor binding sites of SNAI-2 and TCF4 interrupted by HDAC5 variant showed a significant impact of TCF4 on promoter activity of mutated HDAC5. Our findings contribute not only to the identification of unrecognized genetic causes of familial CRC but also underline the importance of 5´UTR variants affecting transcriptional regulation and the pathogenesis of complex disorders.

scholarly journals Whole-Exome Sequencing Characterized the Landscape of Somatic Mutations and Pathways in Colorectal Cancer Liver Metastasis

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Liuxing Feng ◽  
Shifu Hong ◽  
Jin Gao ◽  
Jiayi Li
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Signaling Pathways ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Acid Extraction ◽  
Tumor Mutation Burden ◽  
Colorectal Cancer Liver Metastasis ◽  
Whole Exome ◽  
Mutation Burden

Purpose. Liver metastasis remains the leading cause of cancer-related mortality in colorectal cancer. The mechanism of occurrence and development of liver metastasis from colorectal cancer is unclear. Methods. The primary tumor tissues and blood samples of 8 patients with liver metastasis of colorectal cancer were collected, followed by nucleic acid extraction and library construction. Whole-exome sequencing was performed to detect the genomic variations. Bioinformatics was used to comprehensively analyze the sequencing data of these samples, including the differences of tumor mutation burden, the characteristics of gene mutations, and signaling pathways. Results. The results showed that the top three genes with the highest mutation frequency were TP53, APC, and KRAS. Tumor mutation burden of this study, with a median of 8.34 mutations per MB, was significantly different with The Cancer Genome Atlas databases. Analysis of molecular function and signaling pathways showed that the mutated genes could be classified into five major categories and 39 signaling pathways, involving in Wnt, angiogenesis, P53, Alzheimer disease-presenilin pathway, notch, and cadherin signaling pathway. Conclusions. In conclusion, we identified the extensive landscape of altered genes and pathways in colorectal cancer liver metastasis, which will be useful to design clinical therapy for personalized medicine.

Sign in / Sign up

Export Citation Format

Share Document