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Molecular Characterization of Somatic Alterations in Dukes’ B and C Colorectal Cancers by Targeted Sequencing

Overview of attention for article published in Frontiers in Pharmacology, July 2017
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Title
Molecular Characterization of Somatic Alterations in Dukes’ B and C Colorectal Cancers by Targeted Sequencing
Published in
Frontiers in Pharmacology, July 2017
DOI 10.3389/fphar.2017.00465
Pubmed ID
Authors

Shafina-Nadiawati Abdul, Nurul-Syakima Ab Mutalib, Khor S. Sean, Saiful E. Syafruddin, Muhiddin Ishak, Ismail Sagap, Luqman Mazlan, Isa M. Rose, Nadiah Abu, Norfilza M. Mokhtar, Rahman Jamal

Abstract

Despite global progress in research, improved screening and refined treatment strategies, colorectal cancer (CRC) remains as the third most common malignancy. As each type of cancer is different and exhibits unique alteration patterns, identifying and characterizing gene alterations in CRC that may serve as biomarkers might help to improve diagnosis, prognosis and predict potential response to therapy. With the emergence of next generation sequencing technologies (NGS), it is now possible to extensively and rapidly identify the gene profile of individual tumors. In this study, we aimed to identify actionable somatic alterations in Dukes' B and C in CRC via NGS. Targeted sequencing of 409 cancer-related genes using the Ion Ampliseq(TM) Comprehensive Cancer Panel was performed on genomic DNA obtained from paired fresh frozen tissues, cancer and normal, of Dukes' B (n = 10) and Dukes' C (n = 9) CRC. The sequencing results were analyzed using Torrent Suite, annotated using ANNOVAR and validated using Sanger sequencing. A total of 141 somatic non-synonymous sequence variations were identified in 86 genes. Among these, 64 variants (45%) were predicted to be deleterious, 38 variants (27%) possibly deleterious while the other 39 variants (28%) have low or neutral protein impact. Seventeen genes have alterations with frequencies of ≥10% in the patient cohort and with 14 overlapped genes in both Dukes' B and C. The adenomatous polyposis coli gene (APC) was the most frequently altered gene in both groups (n = 6 in Dukes' B and C). In addition, TP53 was more frequently altered in Dukes' C (n = 7) compared to Dukes' B (n = 4). Ten variants in APC, namely p.R283(∗), p.N778fs, p.R805(∗), p.Y935fs, p.E941fs, p.E1057(∗), p.I1401fs, p.Q1378(∗), p.E1379(∗), and p.A1485fs were predicted to be driver variants. APC remains as the most frequently altered gene in the intermediate stages of CRC. Wnt signaling pathway is the major affected pathway followed by P53, RAS, TGF-β, and PI3K signaling. We reported the alteration profiles in each of the patient which has the potential to affect the clinical decision. We believe that this study will add further to the understanding of CRC molecular landscape.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 23 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 23 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 5 22%
Other 4 17%
Student > Ph. D. Student 3 13%
Student > Bachelor 2 9%
Researcher 2 9%
Other 5 22%
Unknown 2 9%
Readers by discipline Count As %
Medicine and Dentistry 9 39%
Biochemistry, Genetics and Molecular Biology 4 17%
Nursing and Health Professions 2 9%
Agricultural and Biological Sciences 2 9%
Psychology 1 4%
Other 1 4%
Unknown 4 17%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 05 August 2017.
All research outputs
#17,906,525
of 22,990,068 outputs
Outputs from Frontiers in Pharmacology
#7,166
of 16,283 outputs
Outputs of similar age
#225,812
of 314,950 outputs
Outputs of similar age from Frontiers in Pharmacology
#122
of 251 outputs
Altmetric has tracked 22,990,068 research outputs across all sources so far. This one is in the 19th percentile – i.e., 19% of other outputs scored the same or lower than it.
So far Altmetric has tracked 16,283 research outputs from this source. They receive a mean Attention Score of 5.0. This one is in the 48th percentile – i.e., 48% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 314,950 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 23rd percentile – i.e., 23% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 251 others from the same source and published within six weeks on either side of this one. This one is in the 45th percentile – i.e., 45% of its contemporaries scored the same or lower than it.