Comprehensive genomic profiling of malignant phyllodes tumors of the breast
| Autor: | Jeffrey S. Ross, Philip J. Stephens, Kim M. Hirshfield, Siraj M. Ali, Shakti H. Ramkissoon, Sahar Nozad, Julia A. Elvin, Jon Chung, James Suh, Jo-Anne Vergilio, Nadia Dawn Ali, Vincent A. Miller, Alexa B. Schrock, Christine E. Sheehan, Shridar Ganesan |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Oncology Adult Cancer Research medicine.medical_specialty Genomic profiling Adolescent medicine.medical_treatment Breast Neoplasms Malignant phyllodes tumor Disease Targeted therapy MED12 03 medical and health sciences Young Adult 0302 clinical medicine Breast cancer Phyllodes Tumor Internal medicine medicine Cluster Analysis Humans Genetic Predisposition to Disease Aged business.industry Gene Expression Profiling Computational Biology Genetic Variation High-Throughput Nucleotide Sequencing Genomics Middle Aged medicine.disease 030104 developmental biology 030220 oncology & carcinogenesis Mutation Female business |
| Zdroj: | Breast cancer research and treatment. 162(3) |
| ISSN: | 1573-7217 |
| Popis: | Malignant phyllodes tumors (MPT) are exceptionally rare, and the genomic drivers of these tumors are still being elucidated. We performed comprehensive genomic profiling (CGP) of MPT to identify genomic alterations that will inform approaches to targeted therapy for patients with MPT, including relapsed, refractory, and metastatic disease.DNA was extracted from formalin-fixed, paraffin-embedded samples from 24 consecutive patient cases of MPT. CGP was performed using a hybrid capture, adaptor ligation-based next generation sequencing assay to a high, uniform coverage (mean, 582×). Tumor mutational burden (TMB) was calculated from a minimum of 1.14 Mb of sequenced DNA as previously described and reported as mutations/Mb. The results were analyzed for all classes of genomic alterations, including short variants (SV; base substitutions, small insertions, and deletions), rearrangements, and copy number changes, including amplifications and homozygous deletions.The 24 cases of MPT included 15 patients with localized and 9 with metastatic disease. The median TMB was 2.7 mut/Mb, and no cases had a TMB 10 mut/Mb. 20 out of 24 cases were evaluable for microsatellite status, and all were microsatellite stable. The most commonly mutated genes were TP53 (58.3%), TERT-promoter (57.9%), NF1 (45.8%), MED12 (45.8%), CDKN2A/B (33.3%), and MLL2 (33.3%). Targetable kinase fusions including KIAA1549-BRAF or FGFR3-TACC3 were identified in 2/24 (8.3%) tumors.This study identifies clinically relevant genomic alterations that suggest novel targeted therapy approaches for patients with MPT. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink