The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
Identification of Molecular Pathway Aberrations in Uterine Serous Carcinoma by Genome-wide Analyses
Open accessAbstract
BACKGROUND: Uterine cancer is the fourth most common malignancy in women, and uterine serous carcinoma is the most aggressive subtype. However, the molecular pathogenesis of uterine serous carcinoma is largely unknown. We analyzed the genomes of uterine serous carcinoma samples to better understand the molecular genetic characteristics of this cancer. METHODS: Whole-exome sequencing was performed on 10 uterine serous carcinomas and the matched normal blood or tissue samples. Somatically acquired sequence mutations were further verified by Sanger sequencing. The most frequent molecular genetic changes were further validated by Sanger sequencing in 66 additional uterine serous carcinomas and in nine serous endometrial intraepithelial carcinomas (the preinvasive precursor of uterine serous carcinoma) that were isolated by laser capture microdissection. In addition, gene copy number was characterized by single-nucleotide polymorphism (SNP) arrays in 23 uterine serous carcinomas, including 10 that were subjected to whole-exome sequencing. RESULTS: We found frequent somatic mutations in TP53 (81.6%), PIK3CA (23.7%), FBXW7 (19.7%), and PPP2R1A (18.4%) among the 76 uterine serous carcinomas examined. All nine serous carcinomas that had an associated serous endometrial intraepithelial carcinoma had concordant PIK3CA, PPP2R1A, and TP53 mutation status between uterine serous carcinoma and the concurrent serous endometrial intraepithelial carcinoma component. DNA copy number analysis revealed frequent genomic amplification of the CCNE1 locus (which encodes cyclin E, a known substrate of FBXW7) and deletion of the FBXW7 locus. Among 23 uterine serous carcinomas that were subjected to SNP array analysis, seven tumors with FBXW7 mutations (four tumors with point mutations, three tumors with hemizygous deletions) did not have CCNE1 amplification, and 13 (57%) tumors had either a molecular genetic alteration in FBXW7 or CCNE1 amplification. Nearly half of these uterine serous carcinomas (48%) harbored PIK3CA mutation and/or PIK3CA amplification. CONCLUSION: Molecular genetic aberrations involving the p53, cyclin E-FBXW7, and PI3K pathways represent major mechanisms in the development of uterine serous carcinoma.
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Cites
Comprehensive genomic characterization defines human glioblastoma genes and core pathways
The Cancer Genome Atlas Research Network (2008) · Nature · doi:10.1038/nature07385 · Cited by 7,735
The genetic basis of early T-cell precursor acute lymphoblastic leukaemia
Zhang, J., Ding, L., Holmfeldt, L., Wu, G., Heatley, S. L., Payne-Turner, D., Easton, J., Chen, X., Wang, J., Rusch, M., et al. (2012) · Nature · doi:10.1038/nature10725 · Cited by 1,596 · cited 2×
“Specifically, the analysis was run using three different parameters as previously described (13,14): a) a high-quality threshold (minimum quality score set to 20) for pooled tumor and matching normal tissue BAm files; b) a low-quality threshold (minimum quality score set to 10) for pooled tumor and matching normal tis…”
MethodSelf-citationWelcker, M., & Clurman, B. E. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2290 · Cited by 1,084
NCBI Reference Sequences: current status, policy and new initiatives
Pruitt, K. D., Tatusova, T., Klimke, W., & Maglott, D. R. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkn721 · Cited by 736 · cited 2×
“the exome annotation was based on NCBI refSeq (12).”
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Cited by
Therapeutic opportunities within the DNA damage response
Pearl, L. H., Schierz, A. C., Ward, S. E., Al-Lazikani, B., & Pearl, F. M. G. (2015) · Nature Reviews Cancer · doi:10.1038/nrc3891 · Cited by 587
NIH Intramural Sequencing Center (NISC) Comparative Sequencing Program, Le Gallo, M., O'Hara, A. J., Rudd, M. L., Urick, M. E., Hansen, N. F., O'Neil, N. J., Price, J. C., Zhang, S., England, B. M., et al. (2012) · Nature Genetics · doi:10.1038/ng.2455 · Cited by 419
Integrated genomic characterization of endometrial carcinoma
The Cancer Genome Atlas Research Network, & Levine, D. A. (2013) · Nature · doi:10.1038/nature12113 · Cited by 5,784
Clinical actionability of molecular targets in endometrial cancer
Urick, M. E., & Bell, D. W. (2019) · Nature Reviews Cancer · doi:10.1038/s41568-019-0177-x · Cited by 405
Uncovering novel mutational signatures by de novo extraction with SigProfilerExtractor
Islam, S. M. A., Díaz-Gay, M., Wu, Y., Barnes, M., Vangara, R., Bergstrom, E. N., He, Y., Vella, M., Wang, J., Teague, J. W., et al. (2022) · Cell Genomics · doi:10.1016/j.xgen.2022.100179 · Cited by 365
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Metadata
- Authors
- Kuhn, E., Wu, R.-C., Guan, B., Wu, G., Zhang, J., Wang, Y., Song, L., Yuan, X., Wei, L., Roden, R. B. S., Kuo, K.-T., Nakayama, K., Clarke, B., Shaw, P., Olvera, N., Kurman, R. J., Levine, D. A., Wang, T.-L., & Shih, I.-M.
- Venue
- JNCI: Journal of the National Cancer Institute
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-08-23
- Volume
- 104
- Issue
- 19
- Pages
- 1503-1513
- ISSN
- 0027-8874 (ISSN-L)
- 1460-2105
- OpenAlex
- W2166405684
- Cited by
- 247
- References
- 4
- FWCI
- 31.48
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Kuhn, E., Wu, R.-C., Guan, B., Wu, G., Zhang, J., Wang, Y., Song, L., Yuan, X., Wei, L., Roden, R. B. S., Kuo, K.-T., Nakayama, K., Clarke, B., Shaw, P., Olvera, N., Kurman, R. J., Levine, D. A., Wang, T.-L., & Shih, I.-M. (2012). Identification of Molecular Pathway Aberrations in Uterine Serous Carcinoma by Genome-wide Analyses. JNCI: Journal of the National Cancer Institute. https://doi.org/10.1093/jnci/djs345
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