NDLI: The haplotype-resolved genome and epigenome of the aneuploid HeLa cancer cell line

Content Provider	PubMed Central
Author	Adey, Andrew Burton, Joshua N. Kitzman, Jacob O. Hiatt, Joseph B. Lewis, Alexandra P. Martin, Beth K. Qiu, Ruolan Lee, Choli Shendure, Jay
Abstract	The HeLa cell line was established in 1951 from cervical cancer cells taken from a patient, Henrietta Lacks, marking the first successful attempt to continually culture human-derived cells in vitro 1 . HeLa’s robust growth and unrestricted distribution resulted in its broad adoption – both intentionally and through widespread cross-contamination 2 – and for the past sixty years it has served a role analogous to that of a model organism 3 . Its cumulative impact is illustrated by the fact that HeLa is named in >74,000 or ~0.3% of PubMed abstracts. The genomic architecture of HeLa remains largely unexplored beyond its karyotype 4 , in part because like many cancers, its extensive aneuploidy renders such analyses challenging. We performed haplotype-resolved whole genome sequencing 5 of the HeLa CCL-2 strain, discovering point and indel variation, mapping copy-number and loss of heterozygosity (LOH), and phasing variants across full chromosome arms. We further investigated variation and copy-number profiles for HeLa S3 and eight additional strains. Surprisingly, HeLa is relatively stable with respect to point variation, accumulating few new mutations since early passaging. Haplotype resolution facilitated reconstruction of an amplified, highly rearranged region at chromosome 8q24.21 at which the HPV-18 viral genome integrated as the likely initial event underlying tumorigenesis. We combined these maps with RNA-Seq 6 and ENCODE Project 7 datasets to phase the HeLa epigenome, revealing strong, haplotype-specific activation of the proto-oncogene MYC by the integrated HPV-18 genome ~500 kilobases upstream, and permitting 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.
Related Links	http://dx.doi.org/10.1038/nature12064
Ending Page	211
Page Count	5
Starting Page	207
File Format	PDF
ISSN	14764687
e-ISSN	14764687
Journal	Nature
Issue Number	7461
Volume Number	500
Language	English
Publisher Date	2013-08-08
Access Restriction	Open
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

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