File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Genomic characterization of human brain metastases identifies drivers of metastatic lung adenocarcinoma

TitleGenomic characterization of human brain metastases identifies drivers of metastatic lung adenocarcinoma
Authors
Issue Date2020
Citation
Nature Genetics, 2020, v. 52, n. 4, p. 371-377 How to Cite?
AbstractBrain metastases from lung adenocarcinoma (BM-LUAD) frequently cause patient mortality. To identify genomic alterations that promote brain metastases, we performed whole-exome sequencing of 73 BM-LUAD cases. Using case-control analyses, we discovered candidate drivers of brain metastasis by identifying genes with more frequent copy-number aberrations in BM-LUAD compared to 503 primary LUADs. We identified three regions with significantly higher amplification frequencies in BM-LUAD, including MYC (12 versus 6%), YAP1 (7 versus 0.8%) and MMP13 (10 versus 0.6%), and significantly more frequent deletions in CDKN2A/B (27 versus 13%). We confirmed that the amplification frequencies of MYC,YAP1 and MMP13 were elevated in an independent cohort of 105 patients with BM-LUAD. Functional assessment in patient-derived xenograft mouse models validated the notion that MYC, YAP1 or MMP13 overexpression increased the incidence of brain metastasis. These results demonstrate that somatic alterations contribute to brain metastases and that genomic sequencing of a sufficient number of metastatic tumors can reveal previously unknown metastatic drivers.
Persistent Identifierhttp://hdl.handle.net/10722/313987
ISSN
2023 Impact Factor: 31.7
2023 SCImago Journal Rankings: 17.300
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorShih, David J.H.-
dc.contributor.authorNayyar, Naema-
dc.contributor.authorBihun, Ivanna-
dc.contributor.authorDagogo-Jack, Ibiayi-
dc.contributor.authorGill, Corey M.-
dc.contributor.authorAquilanti, Elisa-
dc.contributor.authorBertalan, Mia-
dc.contributor.authorKaplan, Alexander-
dc.contributor.authorD’Andrea, Megan R.-
dc.contributor.authorChukwueke, Ugonma-
dc.contributor.authorIppen, Franziska Maria-
dc.contributor.authorAlvarez-Breckenridge, Christopher-
dc.contributor.authorCamarda, Nicholas D.-
dc.contributor.authorLastrapes, Matthew-
dc.contributor.authorMcCabe, Devin-
dc.contributor.authorKuter, Ben-
dc.contributor.authorKaufman, Benjamin-
dc.contributor.authorStrickland, Matthew R.-
dc.contributor.authorMartinez-Gutierrez, Juan Carlos-
dc.contributor.authorNagabhushan, Deepika-
dc.contributor.authorDe Sauvage, Magali-
dc.contributor.authorWhite, Michael D.-
dc.contributor.authorCastro, Brandyn A.-
dc.contributor.authorHoang, Kaitlin-
dc.contributor.authorKaneb, Andrew-
dc.contributor.authorBatchelor, Emily D.-
dc.contributor.authorPaek, Sun Ha-
dc.contributor.authorPark, Sun Hye-
dc.contributor.authorMartinez-Lage, Maria-
dc.contributor.authorBerghoff, Anna S.-
dc.contributor.authorMerrill, Parker-
dc.contributor.authorGerstner, Elizabeth R.-
dc.contributor.authorBatchelor, Tracy T.-
dc.contributor.authorFrosch, Matthew P.-
dc.contributor.authorFrazier, Ryan P.-
dc.contributor.authorBorger, Darrell R.-
dc.contributor.authorIafrate, A. John-
dc.contributor.authorJohnson, Bruce E.-
dc.contributor.authorSantagata, Sandro-
dc.contributor.authorPreusser, Matthias-
dc.contributor.authorCahill, Daniel P.-
dc.contributor.authorCarter, Scott L.-
dc.contributor.authorBrastianos, Priscilla K.-
dc.date.accessioned2022-07-06T11:28:44Z-
dc.date.available2022-07-06T11:28:44Z-
dc.date.issued2020-
dc.identifier.citationNature Genetics, 2020, v. 52, n. 4, p. 371-377-
dc.identifier.issn1061-4036-
dc.identifier.urihttp://hdl.handle.net/10722/313987-
dc.description.abstractBrain metastases from lung adenocarcinoma (BM-LUAD) frequently cause patient mortality. To identify genomic alterations that promote brain metastases, we performed whole-exome sequencing of 73 BM-LUAD cases. Using case-control analyses, we discovered candidate drivers of brain metastasis by identifying genes with more frequent copy-number aberrations in BM-LUAD compared to 503 primary LUADs. We identified three regions with significantly higher amplification frequencies in BM-LUAD, including MYC (12 versus 6%), YAP1 (7 versus 0.8%) and MMP13 (10 versus 0.6%), and significantly more frequent deletions in CDKN2A/B (27 versus 13%). We confirmed that the amplification frequencies of MYC,YAP1 and MMP13 were elevated in an independent cohort of 105 patients with BM-LUAD. Functional assessment in patient-derived xenograft mouse models validated the notion that MYC, YAP1 or MMP13 overexpression increased the incidence of brain metastasis. These results demonstrate that somatic alterations contribute to brain metastases and that genomic sequencing of a sufficient number of metastatic tumors can reveal previously unknown metastatic drivers.-
dc.languageeng-
dc.relation.ispartofNature Genetics-
dc.titleGenomic characterization of human brain metastases identifies drivers of metastatic lung adenocarcinoma-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1038/s41588-020-0592-7-
dc.identifier.pmid32203465-
dc.identifier.pmcidPMC7136154-
dc.identifier.scopuseid_2-s2.0-85083003496-
dc.identifier.volume52-
dc.identifier.issue4-
dc.identifier.spage371-
dc.identifier.epage377-
dc.identifier.eissn1546-1718-
dc.identifier.isiWOS:000521529000002-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats