Abstract 5740: Identification of genetic signatures in bone metastasis of breast and prostate cancer
Authors: Kähkönen Tiina E. , Halleen Jussi M. , Bernoulli Jenni 
Published: June 2022

Abstract
Bone metastases (BM) cause high mortality and are present in 70-90% of advanced breast and prostate cancer patients. Cancer is a complex genetic disease, and no single gene has been shown to be solely responsible for the initiation, growth or progression of cancer. Therefore, more complete understanding of the multiple genes responsible for disease progression, and more specifically, for the development of BM is needed to support development of diagnostic tools and novel therapeutics for BM.
The aim of this study was to identify genetic signatures specific for BM in solid tumors, more specifically in breast cancer (BC) and prostate cancer (PC).
Genetic data was obtained from cBioPortal. A dataset of 500 metastatic solid tumors was used based on availability of metastasis-specific biopsy data (Robinson et al. Integrative clinical genomics of metastatic cancer, Nature 2017). Altogether 40 of the patients (8%) had BM, of which 27 (67,5%) with PC and 8 (20%) with BC. All cancer biopsy samples were grouped to ‘BM-only’ (n = 40) and ‘no-BM’ (n = 460) groups, indicating the presence or absence of BM. The same comparisons were made separately for BC and PC. To confirm cancer type specificity of the findings, the BC and PC BM-only data were compared. Only significant findings (p&lt;0.05) are reported. Finally, the impact of identified altered genes on clinical outcome (survival) was analyzed more broadly in BC (13 studies, over 7 000 samples) and PC (19 studies, over 6 000 samples) specific datasets.
Altogether 48 genetic alterations including mutations and gene-fusions were identified in BM-only group. From the 48 genes, 8 and 3 corresponded to genetic alterations observed in BC and PC, respectively, when comparing BM-only and no-BM groups. None of these genes overlapped in BC and PC BM-only samples. In BC, the identified 8 genes were GPR139, RASIP1, DTHD1, GGT7, LONP2, ATG4B, PI15 and MKRN3. Of these, GPR139 was associated with improved relapse-free survival, RASIP1 with decreased disease-free survival, GGT7 with improved disease-free survival, and PI15 with lower overall survival when comparing patients with altered or unaltered genes across BC cohorts. In PC, the 3 genes were RNF139, KRTAP4-7 and ZNF516. Of these, RNF139 was associated with decreased overall, disease and progression free survival across PC cohorts.
The study identified four genetic alterations in BC (GPR139, RASIP1, GGT7, PI15) and one in PC (RNF139) that were associated with altered survival in patients. Best to our knowledge, none of these genes have been associated with BM earlier. Further studies are warranted to understand significance of these genes for developing novel therapeutics or diagnostic tools for bone metastatic cancers.
Citation Format: Tiina E. Kähkönen, Jussi M. Halleen, Jenni Bernoulli. Identification of genetic signatures in bone metastasis of breast and prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5740.