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Lee, Semin
Computational Biology Lab
Research Interests
  • Cancer genomics & single-cell genomics

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Integrated genomic and molecular characterization of cervical cancer

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Title
Integrated genomic and molecular characterization of cervical cancer
Author
The Cancer Genome Atlas Research NetworkLee, Semin
Issue Date
201703
Publisher
NATURE PUBLISHING GROUP
Citation
NATURE, v.543, no., pp.378 - 384
Abstract
Cervical cancer remains one of the leading causes of cancer-related deaths worldwide. Here we report the extensive molecular characterization of 228 primary cervical cancers, the largest comprehensive genomic study of cervical cancer to date. We observed striking APOBEC mutagenesis patterns and identified SHKBP1, ERBB3, CASP8, HLA-A, and TGFBR2 as novel significantly mutated genes in cervical cancer. We also discovered novel amplifications in immune targets CD274/PD-L1 and PDCD1LG2/PD-L2, and the BCAR4 lncRNA that has been associated with response to lapatinib. HPV integration was observed in all HPV18-related cases and 76% of HPV16-related cases, and was associated with structural aberrations and increased target gene expression. We identified a unique set of endometrial-like cervical cancers, comprised predominantly of HPV-negative tumors with high frequencies of KRAS, ARID1A, and PTEN mutations. Integrative clustering of 178 samples identified Keratin-low Squamous, Keratin-high Squamous, and Adenocarcinoma-rich subgroups. These molecular analyses reveal new potential therapeutic targets for cervical cancers.
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DOI
http://dx.doi.org/10.1038/nature21386
ISSN
0028-0836
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