دورية أكاديمية
The role of tandem duplicator phenotype in tumour evolution in high-grade serous ovarian cancer.
| العنوان: | The role of tandem duplicator phenotype in tumour evolution in high-grade serous ovarian cancer. |
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| المؤلفون: | Ng CK; Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, UK., Cooke SL, Howe K, Newman S, Xian J, Temple J, Batty EM, Pole JC, Langdon SP, Edwards PA, Brenton JD |
| المصدر: | The Journal of pathology [J Pathol] 2012 Apr; Vol. 226 (5), pp. 703-12. Date of Electronic Publication: 2012 Feb 09. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: John Wiley And Sons Country of Publication: England NLM ID: 0204634 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1096-9896 (Electronic) Linking ISSN: 00223417 NLM ISO Abbreviation: J Pathol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Chichester : John Wiley And Sons Original Publication: London, Oliver & Boyd. |
| مواضيع طبية MeSH: | Gene Duplication* , Mutation* , Tandem Repeat Sequences*, Antineoplastic Agents/*therapeutic use , Drug Resistance, Neoplasm/*genetics , Neoplasms, Cystic, Mucinous, and Serous/*genetics , Ovarian Neoplasms/*drug therapy , Ovarian Neoplasms/*genetics , Platinum Compounds/*therapeutic use, BRCA1 Protein/genetics ; BRCA2 Protein/genetics ; Cell Line, Tumor ; Evolution, Molecular ; Female ; Gene Deletion ; Genetic Predisposition to Disease ; Homologous Recombination ; Humans ; Neoplasm Grading ; Neoplasms, Cystic, Mucinous, and Serous/pathology ; Oligonucleotide Array Sequence Analysis ; Ovarian Neoplasms/pathology ; Phenotype ; Polymorphism, Single Nucleotide ; Sequence Analysis, DNA ; Translocation, Genetic |
| مستخلص: | High-grade serous ovarian carcinoma (HGSOC) is characterized by genomic instability, ubiquitous TP53 loss, and frequent development of platinum resistance. Loss of homologous recombination (HR) is a mutator phenotype present in 50% of HGSOCs and confers hypersensitivity to platinum treatment. We asked which other mutator phenotypes are present in HGSOC and how they drive the emergence of platinum resistance. We performed whole-genome paired-end sequencing on a model of two HGSOC cases, each consisting of a pair of cell lines established before and after clinical resistance emerged, to describe their structural variants (SVs) and to infer their ancestral genomes as the SVs present within each pair. The first case (PEO1/PEO4), with HR deficiency, acquired translocations and small deletions through its early evolution, but a revertant BRCA2 mutation restoring HR function in the resistant lineage re-stabilized its genome and reduced platinum sensitivity. The second case (PEO14/PEO23) had 216 tandem duplications and did not show evidence of HR or mismatch repair deficiency. By comparing the cell lines to the tissues from which they originated, we showed that the tandem duplicator mutator phenotype arose early in progression in vivo and persisted throughout evolution in vivo and in vitro, which may have enabled continual evolution. From the analysis of SNP array data from 454 HGSOC cases in The Cancer Genome Atlas series, we estimate that 12.8% of cases show patterns of aberrations similar to the tandem duplicator, and this phenotype is mutually exclusive with BRCA1/2 carrier mutations. (Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.) |
| معلومات مُعتمدة: | 14545 United Kingdom CRUK_ Cancer Research UK; 15601 United Kingdom CRUK_ Cancer Research UK |
| المشرفين على المادة: | 0 (Antineoplastic Agents) 0 (BRCA1 Protein) 0 (BRCA1 protein, human) 0 (BRCA2 Protein) 0 (BRCA2 protein, human) 0 (Platinum Compounds) |
| تواريخ الأحداث: | Date Created: 20111221 Date Completed: 20120427 Latest Revision: 20240210 |
| رمز التحديث: | 20240210 |
| DOI: | 10.1002/path.3980 |
| PMID: | 22183581 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1096-9896 |
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| DOI: | 10.1002/path.3980 |