scholarly journals Exome sequencing reveals frequent inactivating mutations inARID1A, ARID1B, ARID2andARID4Ain microsatellite unstable colorectal cancer

2014 ◽  
Vol 135 (3) ◽  
pp. 611-623 ◽  
Author(s):  
Tatiana Cajuso ◽  
Ulrika A. Hänninen ◽  
Johanna Kondelin ◽  
Alexandra E. Gylfe ◽  
Tomas Tanskanen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Exome Sequencing ◽  
Inactivating Mutations

Discovery of Aberrant Alteration of Genome in Colorectal Cancer by Exome Sequencing

2019 ◽  
Vol 358 (5) ◽  
pp. 340-349 ◽  
Author(s):  
Yuanzi Liang ◽  
Liejun Jiang ◽  
Xiaogang Zhong ◽  
Steven N. Hochwald ◽  
Yongsi Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Exome Sequencing

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.

Somatic mutations in young-onset colorectal cancer unrelated to hereditary syndromes: A comparative study using high-depth targeted exome sequencing.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 623-623
Author(s):  
Y. Nancy You ◽  
Kyle Chang ◽  
Ken Chen ◽  
Amir Mehdizadeh ◽  
Amanda Cuddy ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Exome Sequencing ◽  
Young Patients ◽  
Cancer Therapeutics ◽  
Metastatic Tumor ◽  
Cancer Center ◽  
Young Onset ◽  
Targeted Exome Sequencing ◽  
Hereditary Syndromes ◽  
Depth Analysis

623 Background: Colorectal cancer (CRC) is being increasingly diagnosed among young adults, but known hereditary syndromes do not account for the majority of these cases. Young patients often present with metastatic disease and exhibit aggressive clinical courses. We aimed to elucidate the potentially unique biology of young-onset CRC. Methods: Patients diagnosed with metastatic CRC prior to age 40 without a known predisposing syndrome (young-onset) were compared to similar patients diagnosed after age 60 (later-onset). Primary and/or metastatic tumor tissues from 19 young- and 51 later-onset patients underwent targeted exome sequencing on a panel of 200 genes using Illumina HiSeq2000 performed by the Institute of Personalized Cancer Therapeutics of MD Anderson Cancer Center. Sequencing was to an average depth of 800x; single nucleotide variations (SNVs) were called according to in-house algorithms. Results: The median age of patients with young-onset CRCs was 34 years (interquartile range: 31-37), while that of later-onset CRCs was 66 years (IQR: 62- 72). The primary CRC was in the rectum in 30% of the young- vs. 16% of the later-onset cases. The overall mutational rate as measured by the number of SNVs per patient (median: 7 vs. 9) did not differ significantly between the groups. However, the median allelic frequency of SNVs was higher in the young-onset group (0.34 vs. 0.17%), suggesting differing patterns of tumor heterogeneity. Genes known to be associated with CRC carcinogenesis were mutated at different proportions (Table); SMAD4, mismatch repair genes (MSH6, MLH1, MSH2), ARID1A, IGF1R and KITappear to be more frequently mutated among the young. Conclusions: This exploratory study suggests that the somatic mutation profiles are distinct between young- vs. later-onset CRCs. More in-depth analysis of the genomic landscape of young-onset CRCs may reveal distinct and novel therapeutic avenues. [Table: see text]

scholarly journals Exome sequencing of a colorectal cancer family reveals shared mutation pattern and predisposition circuitry along tumor pathways

2015 ◽  
Vol 6 ◽  
Author(s):  
Suleiman H. Suleiman ◽  
Mahmoud E. Koko ◽  
Wafaa H. Nasir ◽  
Ommnyiah Elfateh ◽  
Ubai K. Elgizouli ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Exome Sequencing ◽  
Cancer Family ◽  
Mutation Pattern

scholarly journals Identification of Novel Variants in Colorectal Cancer Families by High-Throughput Exome Sequencing

2013 ◽  
Vol 22 (7) ◽  
pp. 1239-1251 ◽  
Author(s):  
Melissa S. DeRycke ◽  
Shanaka R. Gunawardena ◽  
Sumit Middha ◽  
Yan W. Asmann ◽  
Daniel J. Schaid ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Exome Sequencing ◽  
High Throughput ◽  
Novel Variants

scholarly journals Gene discovery in familial cancer syndromes by exome sequencing: prospects for the elucidation of familial colorectal cancer type X

2012 ◽  
Vol 25 (8) ◽  
pp. 1055-1068 ◽  
Author(s):  
Chee-Seng Ku ◽  
David N Cooper ◽  
Mengchu Wu ◽  
Dimitrios H Roukos ◽  
Yudi Pawitan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Exome Sequencing ◽  
Familial Cancer ◽  
Gene Discovery ◽  
Cancer Type ◽  
Familial Colorectal Cancer ◽  
Familial Cancer Syndromes ◽  
Cancer Syndromes

Evolution and heterogeneity of non-hereditary colorectal cancer revealed by single-cell exome sequencing

Oncogene ◽  
2016 ◽  
Vol 36 (20) ◽  
pp. 2857-2867 ◽  
Author(s):  
H Wu ◽  
X-Y Zhang ◽  
Z Hu ◽  
Q Hou ◽  
H Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Single Cell ◽  
Exome Sequencing ◽  
Hereditary Colorectal Cancer

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.

Exome sequencing identifies an MLL3 gene germ line mutation in a pedigree of colorectal cancer and acute myeloid leukemia

Blood ◽  
2013 ◽  
Vol 121 (8) ◽  
pp. 1478-1479 ◽  
Author(s):  
Wei-Dong Li ◽  
Qing-Rong Li ◽  
Shuang-Nian Xu ◽  
Feng-Jiang Wei ◽  
Zhi-Jia Ye ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Acute Myeloid Leukemia ◽  
Exome Sequencing ◽  
Myeloid Leukemia ◽  
Germ Line ◽  
Germ Line Mutation ◽  
Acute Myeloid
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