ORCID Profile
0000-0002-5634-3315
Current Organisations
University Hospital of Zurich
,
Dr. Ram Manohar Lohia Hospital
,
Lausanne University Hospital, Faculty of Biology and Medicine (FBM)
,
Universitat Zurich
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Publisher: Elsevier BV
Date: 03-2021
Publisher: Elsevier BV
Date: 07-2022
Publisher: American Chemical Society (ACS)
Date: 03-10-2023
Publisher: Elsevier BV
Date: 02-2022
Publisher: Springer Science and Business Media LLC
Date: 04-03-2021
DOI: 10.1038/S41467-021-21576-8
Abstract: Although melanoma is initiated by acquisition of point mutations and limited focal copy number alterations in melanocytes-of-origin, the nature of genetic changes that characterise lethal metastatic disease is poorly understood. Here, we analyze the evolution of human melanoma progressing from early to late disease in 13 patients by s ling their tumours at multiple sites and times. Whole exome and genome sequencing data from 88 tumour s les reveals only limited gain of point mutations generally, with net mutational loss in some metastases. In contrast, melanoma evolution is dominated by whole genome doubling and large-scale aneuploidy, in which widespread loss of heterozygosity sculpts the burden of point mutations, neoantigens and structural variants even in treatment-naïve and primary cutaneous melanomas in some patients. These results imply that dysregulation of genomic integrity is a key driver of selective clonal advantage during melanoma progression.
Publisher: American Medical Association (AMA)
Date: 03-2022
Publisher: Elsevier BV
Date: 10-2021
Publisher: Public Library of Science (PLoS)
Date: 15-12-2014
Publisher: Elsevier BV
Date: 2022
Publisher: Elsevier BV
Date: 10-2021
Publisher: Elsevier BV
Date: 09-2022
Publisher: Elsevier BV
Date: 03-2022
Publisher: Springer Science and Business Media LLC
Date: 04-04-2016
DOI: 10.1038/NATURE17392
Publisher: Elsevier BV
Date: 10-2021
Publisher: Elsevier BV
Date: 02-2022
Publisher: Elsevier BV
Date: 10-2021
Publisher: Elsevier BV
Date: 08-2021
Publisher: American Association for Cancer Research (AACR)
Date: 12-03-2015
DOI: 10.1158/1078-0432.CCR-14-2110
Abstract: Purpose: Basal cell carcinomas (BCCs) are tumors ignored by immune surveillance. Activated Hedgehog (Hh) signaling within primary cilia is a key driver in the pathogenesis of BCCs. We examined immune alterations during treatment with systemic Hh inhibitors. Experimental Design: We investigated biopsies from patients with BCC before (23 patients) and after 4 weeks of treatment (5 patients) with Hh signaling inhibitor. Ber-Ep4, BCL-2, Ki-67, CD4, CD8, MHC class I, HLA-DR-class II, and SOX9 were analyzed by immunohistochemistry. Primary cilia were analyzed by double immunofluorescence of acetylated tubulin and SOX9. Differential gene expression for 84 cytokines and chemokines was analyzed in 3 patients. Results: After 4 weeks of treatment, we found reduction of Ki-67, SOX9, Ber-EP4, and BCL-2 expression in tumors associated with morphologic signs of squamous differentiation. In addition, the number of cilia-positive BCC cells was significantly decreased. An upregulation of MHC I expression on the cell membranes of residual tumor cells and an influx of CD4+, HLA-DR-class II+, and CD8+ cells with invasion into the tumor cell nests were found. Finally, qPCR arrays showed the differential expression of genes involved in modulating immune responses. Conclusions: We show that Hh pathway inhibitor–induced tumor regression is accompanied by a dynamic change of the microenvironment with a disruption of immune privilege involving an influx of cytotoxic T cells, activation of the adaptive immune functions, and a profound alteration of the local chemokine/cytokine network. Clin Cancer Res 21(6) 1289–97. ©2015 AACR.
Location: United Kingdom of Great Britain and Northern Ireland
Location: Switzerland
No related grants have been discovered for DR DEEPAK DHAMNETIYA.