Annotation of Genes Having Candidate Somatic Mutations in Acute Myeloid Leukemia with Whole-Exome Sequencing Using Concept Lattice Analysis

Lee, Kye Hwa; Lim, Jae Hyeun; Kim, Ju Han

doi:10.5808/gi.2013.11.1.38

Cited by 2 publications

(1 citation statement)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is located at the long arm of chromosome 6 at position 25. This gene encodes a spectrin repeat containing the nuclear envelope 1 protein expressed in skeletal and smooth muscle and peripheral blood lymphocytes that localizes to the nuclear membrane ( Lee et al, 2013 ). SYNE1 alterations are linked to cerebellar ataxia and have been associated with lung, ovarian, and CRCs ( Doherty et al, 2010 ).…”

Section: Discussionmentioning

confidence: 99%

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

Abdul

Mutalib

Sean³

et al. 2017

Front. Pharmacol.

View full text Add to dashboard Cite

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 AmpliseqTM 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.

show abstract

Section: Discussionmentioning

confidence: 99%

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

Abdul

Mutalib

Sean³

et al. 2017

Front. Pharmacol.

View full text Add to dashboard Cite

show abstract

Identification of somatic mutations using whole-exome sequencing in Korean patients with acute myeloid leukemia

et al. 2017

View full text Add to dashboard Cite

BackgroundAcute myeloid leukemia (AML) is a biologically and clinically heterogeneous cancer of the bone marrow that is characterized by the rapid growth of abnormal myeloid cells.MethodsWe performed a mutational analysis to identify AML somatic mutations using the whole-exome sequencing data of 36 tumor-normal sample pairs from Korean patients with de novo AML. We explored the functional impact of the genes identified in the mutational analyses through an integrated Gene Ontology (GO) and pathway analysis.ResultsA total of 11 genes, including NEFH (p = 6.27 × 10−13 and q = 1.18 × 10−8) and TMPRSS13 (p = 1.40 × 10−10 and q = 1.32 × 10−6), also demonstrated q values less than 0.1 in 36 Korean AML patients. Five out of the 11 novel genes have previously been reported to be associated with other cancers. Two gene mutations, CEBPA (p = 5.22 × 10−5) and ATXN3 (p = 9.75 × 10−4), showed statistical significance exclusively in the M2 and M3 subtypes of the French-American-British classifications, respectively. A total of 501 genes harbored 478 missense, 22 nonsense, 93 frameshift indels, and/or three stop codon deletions and these gene mutations significantly enriched GO terms for signal transduction (GO:0007165, p = 1.77 × 10−3), plasma membrane (GO:0005886, p = 3.07 × 10−4), and scaffold protein binding (GO:0097110, p = 8.65 × 10−4). The mitogen-activated protein kinase (hsa04010, 7.67 × 10−4) was the most enriched Kyoto Encyclopedia of Genes and Genomes pathway.ConclusionsMorphological AML subtypes may in part reflect subtype specific patterns of genomic alterations. Following validation, future studies to evaluate the usefulness of these genes in genetic testing for the early diagnosis and prognostic prediction of AML patients would be worthwhile.Electronic supplementary materialThe online version of this article (doi:10.1186/s12881-017-0382-y) contains supplementary material, which is available to authorized users.

show abstract

Annotation of Genes Having Candidate Somatic Mutations in Acute Myeloid Leukemia with Whole-Exome Sequencing Using Concept Lattice Analysis

Cited by 2 publications

References 27 publications

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

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

Identification of somatic mutations using whole-exome sequencing in Korean patients with acute myeloid leukemia

Contact Info

Product

Resources

About