title: Clonal evolution of acute myeloid leukemia highlighted by latest genome sequencing studies.
abstract: Decades of years might be required for an initiated cell to become a fully-pledged, metastasized tumor. DNA mutations are accumulated during this process including background mutations that emerge scholastically, as well as driver mutations that selectively occur in a handful of cancer genes and confer the cell a growth advantage over its neighbors. A clone of tumor cells could be superseded by another clone that acquires new mutations and grows more aggressively. Tumor evolutional patterns have been studied for years using conventional approaches that focus on the investigation of a single or a couple of genes. Latest deep sequencing technology enables a global view of tumor evolution by deciphering almost all genome aberrations in a tumor. Tumor clones and the fate of each clone during tumor evolution can be depicted with the help of the concept of variant allele frequency. Here, we summarize the new insights of cancer evolutional progression in acute myeloid leukemia. Cancer evolution is currently thought to start from a clone that has accumulated the requisite somatically-acquired genetic aberrations through a series of increasingly disordered clinical and pathological phases, eventually leading to malignant transformation [1-3]. The observations in invasive colorectal cancer that usually emerges from an antecedent benign adenomatous polyp and in cervical cancer that proceeds through intraepithelial neoplasia support the idea of stepwise or linear cancerous progression [3-5]. Genetically, such progression is achieved by successive waves of clonal expansion during which cells acquire novel genomic alterations including single nucleotide variants (SNVs), small insertions and deletions (indels), and/or copy number variations (CNVs) [6]. The latest improvement in sequencing technology has allowed the deciphering of the whole exome or genome in different types of tumor and normal tissue pairs, providing detailed catalogue about genome aberrations during tumor initiation and progression, which have been reviewed in several papers [7-10]. Here, we focus on demonstrating the cancer clonal evolution pattern revealed by recent deep sequencing studies of samples from acute myeloid leukemia (AML) patients.
authors.affiliation: Center of Genome and Personalized Medicine, Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Dalian, China.
authors.forename: Xuehong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Center of Genome and Personalized Medicine, Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Dalian, China.
authors.forename: Dekang
authors.initials: D
authors.lastname: Lv
authors.affiliation: Center of Genome and Personalized Medicine, Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Dalian, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Center of Genome and Personalized Medicine, Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Dalian, China.|State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, China.|Department of Hematology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.|Institute of Hematology, Sun Yat-sen University, Guangzhou, China.
authors.forename: Quentin
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Center of Genome and Personalized Medicine, Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Dalian, China.
authors.forename: Zhiguang
authors.initials: Z
authors.lastname: Li
mesh_terms: D002869:Chromosome Aberrations; D060965:Clonal Evolution; D056915:DNA Copy Number Variations; D059472:Exome; D005260:Female; D005787:Gene Frequency; D015894:Genome, Human; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006579:Heterozygote; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D009154:Mutation; D009362:Neoplasm Metastasis; D017422:Sequence Analysis, DNA
keywords: acute myeloid leukemia; cancer genome; clonal evolution