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Comprehensive genomic profiling of malignant phyllodes tumors of the breast.
Breast Cancer Res Treat 2017; 162(3):597-602BC

Abstract

PURPOSE

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

This study identifies clinically relevant genomic alterations that suggest novel targeted therapy approaches for patients with MPT.

Authors+Show Affiliations

Albany Medical College, Albany, NY, USA.Albany Medical College, Albany, NY, USA.Foundation Medicine, Inc., Cambridge, MA, USA.Foundation Medicine, Inc., Cambridge, MA, USA.Foundation Medicine, Inc., Cambridge, MA, USA.Foundation Medicine, Inc., Cambridge, MA, USA.Foundation Medicine, Inc., Cambridge, MA, USA.Foundation Medicine, Inc., Cambridge, MA, USA.Division of Medical Oncology, Department of Medicine, Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, NJ, USA.Division of Medical Oncology, Department of Medicine, Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, NJ, USA.Division of Medical Oncology, Department of Medicine, Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, NJ, USA.Foundation Medicine, Inc., Cambridge, MA, USA.Foundation Medicine, Inc., Cambridge, MA, USA.Foundation Medicine, Inc., Cambridge, MA, USA.Albany Medical College, Albany, NY, USA. jross@foundationmedicine.com. Foundation Medicine, Inc., Cambridge, MA, USA. jross@foundationmedicine.com. Department of Pathology and Laboratory Medicine, Albany Medical College, 47 New Scotland Ave, Albany, NY, 12208, USA. jross@foundationmedicine.com.Foundation Medicine, Inc., Cambridge, MA, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28210881

Citation

Nozad, Sahar, et al. "Comprehensive Genomic Profiling of Malignant Phyllodes Tumors of the Breast." Breast Cancer Research and Treatment, vol. 162, no. 3, 2017, pp. 597-602.
Nozad S, Sheehan CE, Gay LM, et al. Comprehensive genomic profiling of malignant phyllodes tumors of the breast. Breast Cancer Res Treat. 2017;162(3):597-602.
Nozad, S., Sheehan, C. E., Gay, L. M., Elvin, J. A., Vergilio, J. A., Suh, J., ... Chung, J. H. (2017). Comprehensive genomic profiling of malignant phyllodes tumors of the breast. Breast Cancer Research and Treatment, 162(3), pp. 597-602. doi:10.1007/s10549-017-4156-1.
Nozad S, et al. Comprehensive Genomic Profiling of Malignant Phyllodes Tumors of the Breast. Breast Cancer Res Treat. 2017;162(3):597-602. PubMed PMID: 28210881.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comprehensive genomic profiling of malignant phyllodes tumors of the breast. AU - Nozad,Sahar, AU - Sheehan,Christine E, AU - Gay,Laurie M, AU - Elvin,Julia A, AU - Vergilio,Jo-Anne, AU - Suh,James, AU - Ramkissoon,Shakti, AU - Schrock,Alexa B, AU - Hirshfield,Kim M, AU - Ali,Nadia, AU - Ganesan,Shridar, AU - Ali,Siraj M, AU - Miller,Vincent A, AU - Stephens,Philip J, AU - Ross,Jeffrey S, AU - Chung,Jon H, Y1 - 2017/02/17/ PY - 2017/02/08/received PY - 2017/02/10/accepted PY - 2017/2/18/pubmed PY - 2017/12/8/medline PY - 2017/2/18/entrez KW - Comprehensive genomic profiling KW - MED12 KW - Malignant phyllodes tumor KW - NF1 KW - Targeted therapy SP - 597 EP - 602 JF - Breast cancer research and treatment JO - Breast Cancer Res. Treat. VL - 162 IS - 3 N2 - PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: This study identifies clinically relevant genomic alterations that suggest novel targeted therapy approaches for patients with MPT. SN - 1573-7217 UR - https://www.unboundmedicine.com/medline/citation/28210881/Comprehensive_genomic_profiling_of_malignant_phyllodes_tumors_of_the_breast_ L2 - https://doi.org/10.1007/s10549-017-4156-1 DB - PRIME DP - Unbound Medicine ER -