@article {158958, title = {Assessing germline mutational profile and its clinicopathological associations in Triple Negative Breast Cancer.}, journal = {Cancer Genet}, volume = {296-297}, year = {2025}, month = {2025 Jun 18}, pages = {65-75}, abstract = {

BACKGROUND: Breast cancer is the most common cancer in Indian women with a high incidence of triple negative breast cancer (TNBC). The high TNBC prevalence (\>25 \%) in India remains a challenge in clinical management. Association of germline BRCA1/2 mutations in TNBCs is well-established as a predisposing factor for hereditary breast cancer risk. These studies are, however, predominantly representative of western population. Therefore, we investigated germline profiles of multi-institutional cohort of TNBC patients in India METHODS: Multigene NGS (next-generation sequencing) panel testing of Triple Negative Breast Cancer patients was conducted. All patients were offered pre-test and post-test counseling.

RESULTS: In our study cohort of 192 TNBC patients, median age at diagnosis was 47 years (23-78). Germline pathogenic mutations were identified in 28.6 \% cases. Of the 58 pathogenic mutations identified, BRCA1 accounted for 72.4 \% and BRCA2 for 13.8 \%. Eight pathogenic mutations were identified in non-BRCA genes associated with DNA damage response pathway. Ten novel mutations were identified in 3 genes namely BRCA1, BRCA2 and PALB2. Comparison of allele-frequency with the global databases like TCGA (The Cancer Genome Atlas), gnomAD and Genome Asia 100 K indicated that the novel mutations were unique.

CONCLUSIONS: Our study confirms the major proportion of mutations in BRCA1/2 genes in TNBCs in India. Interestingly, a higher proportion of VUS were found in the non-BRCA genes compared to BRCA1/2 emphasizing the need for functional studies of the non-BRCA genes. Large scale studies are warranted to elucidate the landscape of germline mutations relevant to the Indian population and their probable clinical implications.

}, issn = {2210-7762}, doi = {10.1016/j.cancergen.2025.06.004}, author = {John, Jisha and Bapat, Ashwini and Gahlaut, Siddharth and Luke, Naveen and Kumar, Rahul and Thakur, Yashaswi and Mathew, Christina and Konnur, Aishwarya and Namewar, Namrata and Reddy, Ruhi and Nagarkar, Sanket and Nare, Smeeta and Thomas, George and Busheri, Laleh and Reddy, Asha and Kelkar, Devaki and Dixit, Santosh and Deshmukh, Chetan and Ul Mannan, Ashraf and Sabarinathan, Radhakrishnan and Radhakrishna, Selvi and Mishra, Rupa and Koppiker, Chaitanyanand B} } @article {128078, title = {Prognostic association of immunoproteasome expression in solid tumours is governed by the immediate immune environment.}, journal = {Mol Oncol}, year = {2023}, month = {2023 Apr 25}, abstract = {

Induction of immunoproteasome (IP) expression in tumour cells can enhance antigen presentation and immunogenicity. Recently, the overexpression of IP genes has been associated with better prognosis and response to immune checkpoint blockade (ICB) therapies in melanoma. However, the extent of this association in other solid tumours and how that is influenced by tumour cell-intrinsic and cell-extrinsic factors remain unclear. Here, we address this by exploring the gene expression patterns from available bulk and single-cell transcriptomic data of primary tumours. We find that tumours with high-IP expression exhibit cytotoxic immune cell infiltration and upregulation of IFN-γ and TNF-α pathways in tumour cells. However, the association of IP expression with overall survival (TCGA cohort) and response to ICB therapy (non-TCGA cohorts) is tumour-type specific (better in non-small-cell lung, breast, bladder and thymus; and worse in glioma and renal) and is greatly influenced by pro- or antitumourigenic immune cell infiltration patterns. This emphasises the need for considering immune cell infiltration patterns, along with IP expression, as a prognostic biomarker to predict overall survival or response to ICB therapies in solid tumours, besides melanoma.

}, issn = {1878-0261}, doi = {10.1002/1878-0261.13443}, author = {Kumar, Rahul and Dhaka, Bhavya and Sahoo, Sarthak and Jolly, Mohit Kumar and Sabarinathan, Radhakrishnan} }