Integrated DNA and RNA Sequencing Reveals Drivers of Endocrine Resistance in Estrogen Receptor-Positive Breast Cancer (Record no. 787)
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042 ## - AUTHENTICATION CODE | |
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Authentication code | dc |
100 10 - MAIN ENTRY--PERSONAL NAME | |
Personal name | Xia, Youli |
Relator term | author |
9 (RLIN) | 1280 |
245 00 - TITLE STATEMENT | |
Title | Integrated DNA and RNA Sequencing Reveals Drivers of Endocrine Resistance in Estrogen Receptor-Positive Breast Cancer |
260 ## - PUBLICATION, DISTRIBUTION, ETC. | |
Name of publisher, distributor, etc. | American Association for Cancer Research, |
Date of publication, distribution, etc. | 2022-08-15. |
500 ## - GENERAL NOTE | |
General note | /pmc/articles/PMC7613305/ |
500 ## - GENERAL NOTE | |
General note | /pubmed/35653148 |
520 ## - SUMMARY, ETC. | |
Summary, etc. | PURPOSE: Endocrine therapy resistance (ETR) remains the greatest challenge in treating patients with hormone receptor-positive breast cancer. We set out to identify molecular mechanisms underlying ETR through in-depth genomic analysis of breast tumors. EXPERIMENTAL DESIGN: We collected pre-treatment and sequential on-treatment tumor samples from 35 patients with estrogen receptor-positive breast cancer treated with neoadjuvant then adjuvant endocrine therapy; 3 had intrinsic resistance, 19 acquired resistance, and 13 remained sensitive. Response was determined by changes in tumor volume neoadjuvantly and by monitoring for adjuvant recurrence. Twelve patients received two or more lines of endocrine therapy, with subsequent treatment lines being initiated at the time of development of resistance to the previous endocrine therapy. DNA whole-exome sequencing and RNA sequencing were performed on all samples, totalling 169 unique specimens. DNA mutations, copy-number alterations, and gene expression data were analyzed through unsupervised and supervised analyses to identify molecular features related to ETR. RESULTS: Mutations enriched in ETR included ESR1 and GATA3. The known ESR1 D538G variant conferring ETR was identified, as was a rarer E380Q variant that confers endocrine hypersensitivity. Resistant tumors which acquired resistance had distinct gene expression profiles compared with paired sensitive tumors, showing elevated pathways including ER, HER2, GATA3, AKT, RAS, and p63 signaling. Integrated analysis in individual patients highlighted the diversity of ETR mechanisms. CONCLUSIONS: The mechanisms underlying ETR are multiple and characterized by diverse changes in both somatic genetic and transcriptomic profiles; to overcome resistance will require an individualized approach utilizing genomic and genetic biomarkers and drugs tailored to each patient. |
540 ## - TERMS GOVERNING USE AND REPRODUCTION NOTE | |
Terms governing use and reproduction | ©2022 The Authors; Published by the American Association for Cancer Research |
540 ## - TERMS GOVERNING USE AND REPRODUCTION NOTE | |
Terms governing use and reproduction | https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) license. |
546 ## - LANGUAGE NOTE | |
Language note | en |
690 ## - LOCAL SUBJECT ADDED ENTRY--TOPICAL TERM (OCLC, RLIN) | |
Topical term or geographic name as entry element | Translational Cancer Mechanisms and Therapy |
9 (RLIN) | 1292 |
655 7# - INDEX TERM--GENRE/FORM | |
Genre/form data or focus term | Text |
Source of term | local |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | He, Xiaping |
Relator term | author |
9 (RLIN) | 1281 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Renshaw, Lorna |
Relator term | author |
9 (RLIN) | 1282 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Martinez-Perez, Carlos |
Relator term | author |
9 (RLIN) | 1283 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Kay, Charlene |
Relator term | author |
9 (RLIN) | 1284 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Gray, Mark |
Relator term | author |
9 (RLIN) | 1285 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Meehan, James |
Relator term | author |
9 (RLIN) | 1286 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Parker, Joel S. |
Relator term | author |
9 (RLIN) | 1287 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Perou, Charles M. |
Relator term | author |
9 (RLIN) | 1288 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Carey, Lisa A. |
Relator term | author |
9 (RLIN) | 1289 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Dixon, J. Michael |
Relator term | author |
9 (RLIN) | 1290 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Turnbull, Arran |
Relator term | author |
9 (RLIN) | 1291 |
786 0# - DATA SOURCE ENTRY | |
Note | Clin Cancer Res |
856 41 - ELECTRONIC LOCATION AND ACCESS | |
Uniform Resource Identifier | <a href="http://dx.doi.org/10.1158/1078-0432.CCR-21-3189">http://dx.doi.org/10.1158/1078-0432.CCR-21-3189</a> |
Public note | Connect to this object online. |
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