Scopus
YÖKSİS Eşleşti
Identifying Genomic Alterations in Patients With Stage IV Breast Cancer Using MammaSeq: An International Collaborative Study
Clinical Breast Cancer · Haziran 2021
YÖKSİS Kayıtları
Identifying Genomic Alterations in Patients With Stage IV Breast Cancer Using MammaSeq: An International Collaborative Study
CLINICAL BREAST CANCER · 2021 SCI
PROFESÖR NEVZAT SERDAR UĞRAŞ →
Makale Bilgileri
DergiClinical Breast Cancer
Yayın TarihiHaziran 2021
Cilt / Sayfa21 · 210-217
Scopus ID2-s2.0-85096139809
Özet
Background: Identification of genomic alterations present in cancer patients may aid in cancer diagnosis, prognosis and therapeutic target discovery. In this study, we aimed to identify clinically actionable variants present in stage IV breast cancer (BC) samples. Materials and Methods: DNA was extracted from formalin-fixed paraffin-embedded samples of BC (n = 41). DNA was sequenced using MammaSeq, a BC-specific next-generation sequencing panel targeting 79 genes and 1369 mutations. Ion Torrent Suite 4.0 was used to make variant calls on the raw data, and the resulting single nucleotide variants were annotated using the CRAVAT toolkit. Single nucleotide variations (SNVs) were filtered to remove common polymorphisms and germline variants. CNVkit was employed to identify copy number variations (CNVs). The Precision Medicine Knowledgebase (PMKB) and OncoKB Precision Oncology Database were used to associate clinical significance with the identified variants. Results: A total of 41 samples from Turkish patients with BC were sequenced (read depth of 94-13,340; median of 1529). These patients were diagnosed with various BC subtypes including invasive ductal carcinoma, invasive lobular carcinoma, apocrine BC, and micropapillary BC. In total, 59 different alterations (49 SNVs and 10 CNVs) were identified. From these, 8 alterations (3 CNVs – ERBB2, FGFR1, and AR copy number gains and 5 SNVs – IDH1.R132H, TP53.E204∗, PI3KCA.E545K, PI3KCA.H1047R, and PI3KCA.R88Q) were identified to have some clinical significance by PMKB and OncoKB. Moreover, the top 5 genes with the most SNVs included PIK3CA, TP53, MAP3K1, ATM, and NCOR1. Additionally, copy number gains and losses were found in ERBB2, GRB7, IGFR1, AR, FGFR1, MYC, and IKBKB, and BRCA2, RUNX1, and RB1, respectively. Conclusion: We identified 59 unique alterations in 38 genes in 41 stage IV BC tissue samples using MammaSeqTM. Eight of these alterations were found to have some clinical significance by OncoKB and PKMB. This study highlights the potential use of cancer specific next-generation sequencing panels in clinic to get better insight into the patient-specific genomic alterations.
Yazarlar (8)
1
Osama Shiraz Shah
ORCID: 0000-0003-4756-4535
2
Atilla Soran
3
Mustafa Şahin
4
Beth A. Knapick
5
Serdar Uğraş
6
Zeliha Esin Celik
7
Peter C. Lucas
8
Adrian V. Lee
ORCID: 0000-0001-9917-514X
Anahtar Kelimeler
Clinical genomics
Clinical utility
NGS panel
Targeted next generation sequencing
Turkish population
Kurumlar
Magee-Womens Research Institute
Pittsburgh United States
Selçuk Üniversitesi
Selçuklu Turkey
University of Pittsburgh
Pittsburgh United States
University of Pittsburgh Medical Center
Pittsburgh United States
University of Pittsburgh School of Medicine
Pittsburgh United States
UPMC Hillman Cancer Center
Pittsburgh United States
Metrikler
2
Atıf
8
Yazar
5
Anahtar Kelime