PMC:3630385 / 1473-4341 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/3630385","sourcedb":"PMC","sourceid":"3630385","source_url":"https://www.ncbi.nlm.nih.gov/pmc/3630385","text":"Introduction\nAcute myeloid leukemia (AML), which is characterized by the rapid growth of abnormal myeloid cells in the marrow, is a highly malignant and cytogenetically heterogeneous type of cancer [1]. AML is categorized into three risk groups: favorable, intermediate, and unfavorable. AML with a normal karyotype (NK-AML) accounts for approximately 40% to 50% of adult patients and 25% of pediatric patients with AML and is composed of a heterogeneous group with an intermediate prognosis [2].\nIn the past few years, next-generation sequencing technologies have been developed rapidly in the field of cancer genomics [3, 4] and enabled a direct genome-wide association test for NK-AML at single-base resolution in an unbiased manner [5]. A comprehensive understanding of the genetic lesions is an important basis for developing personalized therapies for the treatment of NK-AML [6].\nLey et al. [5] carried out the first whole-genome association study for AML by using single-end whole-genome sequencing data and found 181 single nucleotide variations (SNVs), including 28 indels, nonsynonymous, and splicing sites (NPM1 and FLT3, respectively). Mardis et al. [7] performed paired-end whole-genome sequencing for cytogenetically normal AML, found seven nonsynonymous SNVs (nsSNVs), one splice site SNV, two indels in coding regions, and 52 somatic point mutations in conserved or regulatory genomic regions, and observed a 10% recurrence rate in the IDH1 mutation in 188 additional AML samples. In the following year, Ley et al. [5] carried out a case-control study of relapsed AML among patients who were reported in 2008. They found a one-base-pair deletion in the DNMT3A gene, which showed a recurrence risk of 22% in AML [8]. De Weer et al. [9] detected deletions within a chromosomal region of 7q35-q36, which contains the CNTNAP2 gene, in both Kasumi-3 and MUTZ-3 cell lines using high-resolution array comparative genomic hybridization (CGH). Particularly, Bejar et al. [10] identified novel associations between somatic mutations in two genes, ETV6 and GNAS, and both myelodysplastic syndrome (previously known as preleukemia) and AML using high-throughput genotyping technology. In the same year, Link et al. [11] identified a novel TP53 susceptibility mutation in AML patients through the use of whole-genome sequencing. Recent exome-sequencing studies found more than 60 susceptible variants, including indels and splicing site mutations, in AML patients [12]. However, to the best of our knowledge, none of the previous studies attempted to predict the risk of NK-AML by analyzing whole-exome sequencing data.\nThis study aimed to evaluate the effect of nsSNVs in 10 pairs of tumor and normal cells of NK-AML patients with whole-exome sequencing data. Finally, we developed genetic risk prediction models for NK-AML by creating genetic risk scores (GRS).","divisions":[{"label":"Title","span":{"begin":0,"end":12}}],"tracks":[{"project":"2_test","denotations":[{"id":"23613682-10502596-44836336","span":{"begin":199,"end":200},"obj":"10502596"},{"id":"23613682-16960150-44836337","span":{"begin":493,"end":494},"obj":"16960150"},{"id":"23613682-19360079-44836338","span":{"begin":621,"end":622},"obj":"19360079"},{"id":"23613682-23105932-44836339","span":{"begin":624,"end":625},"obj":"23105932"},{"id":"23613682-18987736-44836340","span":{"begin":737,"end":738},"obj":"18987736"},{"id":"23613682-22666660-44836341","span":{"begin":883,"end":884},"obj":"22666660"},{"id":"23613682-18987736-44836342","span":{"begin":899,"end":900},"obj":"18987736"},{"id":"23613682-19657110-44836343","span":{"begin":1164,"end":1165},"obj":"19657110"},{"id":"23613682-18987736-44836344","span":{"begin":1533,"end":1534},"obj":"18987736"},{"id":"23613682-21067377-44836345","span":{"begin":1729,"end":1730},"obj":"21067377"},{"id":"23613682-20084277-44836346","span":{"begin":1749,"end":1750},"obj":"20084277"},{"id":"23613682-21714648-44836347","span":{"begin":1981,"end":1983},"obj":"21714648"},{"id":"23613682-21505135-44836348","span":{"begin":2222,"end":2224},"obj":"21505135"},{"id":"23613682-21399634-44836349","span":{"begin":2470,"end":2472},"obj":"21399634"}],"attributes":[{"subj":"23613682-10502596-44836336","pred":"source","obj":"2_test"},{"subj":"23613682-16960150-44836337","pred":"source","obj":"2_test"},{"subj":"23613682-19360079-44836338","pred":"source","obj":"2_test"},{"subj":"23613682-23105932-44836339","pred":"source","obj":"2_test"},{"subj":"23613682-18987736-44836340","pred":"source","obj":"2_test"},{"subj":"23613682-22666660-44836341","pred":"source","obj":"2_test"},{"subj":"23613682-18987736-44836342","pred":"source","obj":"2_test"},{"subj":"23613682-19657110-44836343","pred":"source","obj":"2_test"},{"subj":"23613682-18987736-44836344","pred":"source","obj":"2_test"},{"subj":"23613682-21067377-44836345","pred":"source","obj":"2_test"},{"subj":"23613682-20084277-44836346","pred":"source","obj":"2_test"},{"subj":"23613682-21714648-44836347","pred":"source","obj":"2_test"},{"subj":"23613682-21505135-44836348","pred":"source","obj":"2_test"},{"subj":"23613682-21399634-44836349","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#93d2ec","default":true}]}]}}