HeLa癌细胞系（生物医学研究中使用时间最长、同时也应当是使用最普遍的人细胞系）的首次基因组定性，显示了一个对“点突变”和版本数改变来说都惊人地稳定的基因组。“点突变”率也许并不高于正常组织的体细胞突变率，同时能将在上个世纪50年代彼此分开的不同HeLa细胞系的基因组区分开来的版本数改变也非常少。本文作者通过将几个数据集（其中包括来自ENCODE项目的数据集）整合起来研究了基因剂量和表达之间的关系，同时发现了MYC原致癌基因由于“18-型人乳头状病毒” (HPV-18) 在“染色体8q24.21”上的集成而受到的强烈激活。（生物谷Bioon.com）
生物谷推荐英文摘要：
Nature doi: 10.1038/nature12064
The haplotype-resolved genome and epigenome of the aneuploid HeLa cancer cell line
Andrew Adey, Joshua N. Burton, Jacob O. Kitzman, Joseph B. Hiatt, Alexandra P. Lewis, Beth K. Martin, Ruolan Qiu, Choli Lee & Jay Shendure
The HeLa cell line was established in 1951 from cervical cancer cells taken from a patient, Henrietta Lacks. This was the first successful attempt to immortalize human-derived cells in vitro. The robust growth and unrestricted distribution of HeLa cells resulted in its broad adoption—both intentionally and through widespread cross-contamination—and for the past 60?years it has served a role analogous to that of a model organism. The cumulative impact of the HeLa cell line on research is demonstrated by its occurrence in more than 74,000 PubMed abstracts (approximately 0.3%). The genomic architecture of HeLa remains largely unexplored beyond its karyotype, partly because like many cancers, its extensive aneuploidy renders such analyses challenging. We carried out haplotype-resolved whole-genome sequencing of the HeLa CCL-2 strain, examined point- and indel-mutation variations, mapped copy-number variations and loss of heterozygosity regions, and phased variants across full chromosome arms. We also investigated variation and copy-number profiles for HeLa S3 and eight additional strains. We find that HeLa is relatively stable in terms of point variation, with few new mutations accumulating after early passaging. Haplotype resolution facilitated reconstruction of an amplified, highly rearranged region of chromosome 8q24.21 at which integration of the human papilloma virus type 18 (HPV-18) genome occurred and that is likely to be the event that initiated tumorigenesis. We combined these maps with RNA-seq and ENCODE Project data sets to phase the HeLa epigenome. This revealed strong, haplotype-specific activation of the proto-oncogene MYC by the integrated HPV-18 genome approximately 500 kilobases upstream, and enabled global analyses of the relationship between gene dosage and expression. These data provide an extensively phased, high-quality reference genome for past and future experiments relying on HeLa, and demonstrate the value of haplotype resolution for characterizing cancer genomes and epigenomes.
