Response to angiotensin blockade with irbesartan in a patient with metastatic colorectal cancer

Jones, Martin; Schrader, Kasmintan A.; Shen, Yaoqing; Pleasance, Erin; Ch’ng, Carolyn; Dar, Nazir Ahmad; Yip, Steven; Renouf, Daniel J.; Schein, Jacquie; Mungall, Andrew J.; Zhao, Yong; Moore, Richard A.; Ma, Yusanne; Sheffield, Brandon S.; Ng, Tony; Jones, Steven J.M.; Marra, Marco A.; Laskin, Janessa; Lim, Howard John

doi:10.1093/annonc/mdw060

Cited by 40 publications

(25 citation statements)

References 27 publications

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“…Paired-end reads (125 bp for genome sequencing, 75 bp for transcriptome sequencing) were generated on an Illumina HiSeq2500 sequencer (Illumina Inc.; ). Tumor biopsy and peripheral blood samples were sequenced to a depth of 93× and 46×, respectively, using established polymerase chain reaction (PCR)-free whole-genome sequencing and strand-specific RNA-seq protocols previously described ( Jones et al 2016 ). More than 267 million passed filter reads were obtained from the RNA-seq experiment.…”

Section: Methodsmentioning

confidence: 99%

Genomic profiling of pelvic genital type leiomyosarcoma in a woman with a germlineCHEK2:c.1100delC mutation and a concomitant diagnosis of metastatic invasive ductal breast carcinoma

Thibodeau

Reisle

Zhao

et al. 2017

Cold Spring Harb Mol Case Stud

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We describe a woman with the known pathogenic germline variant CHEK2:c.1100delC and synchronous diagnoses of both pelvic genital type leiomyosarcoma (LMS) and metastatic invasive ductal breast carcinoma. CHEK2 (checkpoint kinase 2) is a tumor-suppressor gene encoding a serine/threonine-protein kinase (CHEK2) involved in double-strand DNA break repair and cell cycle arrest. The CHEK2:c.1100delC variant is a moderate penetrance allele resulting in an approximately twofold increase in breast cancer risk. Whole-genome and whole-transcriptome sequencing were performed on the leiomyosarcoma and matched blood-derived DNA. Despite the presence of several genomic hits within the double-strand DNA damage pathway (CHEK2 germline variant and multiple RAD51B somatic structural variants), tumor profiling did not show an obvious DNA repair deficiency signature. However, even though the LMS displayed clear malignant features, its genomic profiling revealed several characteristics classically associated with leiomyomas including a translocation, t(12;14), with one breakpoint disrupting RAD51B and the other breakpoint upstream of HMGA2 with very high expression of HMGA2 and PLAG1. This is the first report of LMS genomic profiling in a patient with the germline CHEK2:c.1100delC variant and an additional diagnosis of metastatic invasive ductal breast carcinoma. We also describe a possible mechanistic relationship between leiomyoma and LMS based on genomic and transcriptome data. Our findings suggest that RAD51B translocation and HMGA2 overexpression may play an important role in LMS oncogenesis.

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Section: Methodsmentioning

confidence: 99%

Genomic profiling of pelvic genital type leiomyosarcoma in a woman with a germlineCHEK2:c.1100delC mutation and a concomitant diagnosis of metastatic invasive ductal breast carcinoma

Thibodeau

Reisle

Zhao

et al. 2017

Cold Spring Harb Mol Case Stud

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“…Its related biological functions are based on the inflammatory response, IL-6/JAK/Stat3/NRF2 signaling pathway, epithelial-mesenchymal transition process and autophagy [41,42]. JUN gene encodes a protein highly similar to the viral protein which was demonstrated to be involved in human malignant disease such as hepatocellular carcinoma, acute myeloid leukemia, colorectal cancer, breast cancer, B-cell lymphomas [43][44][45][46][47][48]. However, few reports associated with pancreatic cancer cells or PSCs which might be a novel research direction for PDAC.…”

Section: Discussionmentioning

confidence: 99%

Identification of key pathways and genes changes in pancreatic cancer cells (BXPC-3) after cross-talk with primary pancreatic stellate cells using bioinformatics analysis

Tang

Zhou

et al. 2019

neo

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Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant tumors with poor prognosis, and the interaction between activated pancreatic stellate cells (PSCs) and PDAC cells plays an important role in the development of PDAC. The aim of this study was to identify gene changes in BXPC-3 after cross-talk with PSCs and reveal their potential mechanisms. The gene expression profiling analysis of BXPC-3 was completed after co-culture with primary PSCs for 48 h. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed, and the differentially expressed genes (DEGs) were identified by Agilent GeneSpring GX software. In total, 3657 DEGs were identified in BXPC-3, including 1881 up-regulated genes and 1776 downregulated genes. GO analysis results showed that upregulated DEGs were significantly enriched in biological processes (BP), including peptide metabolic process, response to stress and electron transport chain; the downregulated DEGs were significantly enriched in biological processes, including signaling, multicellular organism development and anatomical structure development. KEGG pathway analysis revealed that 19 pathways were upregulated and 32 pathways were downregulated, and that upregulated DEGs were enriched in protein export and glutathione metabolism, while the downregulated DEGs were enriched in axon guidance and focal adhesion. The top 10 upregulated genes and the top 10 downregulated genes were identified. By constructing PPI network, we selected out 10 key genes (TP53, SRC, IL6, JUN, ISG15, CAD, STAT1, OAS3, OAS1, VIM) and significant pathways. The associated survival analysis was performed and the SRC, IL-6, ISG15, STAT1, OAS3, OAS1 and VIM were proved to be related to worse overall survival time of PDAC patients. In conclusion, the present study indicated that the identified DEGs promote our understanding of the molecular mechanisms underlying the interaction between pancreatic cancer cells and PSCs and might be used as molecular targets in the future to study the role of tumor microenvironment in the progression of PDAC.

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“…The positive outcome of such approaches is already being realized in the field of oncology. For instance, a recent case report on a patient with metastatic colorectal cancer, treatment-related toxicity, and resistance to chemotherapy and radiation [24] seems particularly relevant in relation to drug repurposing. The patient underwent immunohistochemical analysis for expression of the MMR proteins MSH2, MSH6, PMS2, and MLH1 and the V600E mutant BRAF protein.…”

Section: Precision Medicinementioning

confidence: 99%

Challenges and opportunities with drug repurposing: finding strategies to find alternative uses of therapeutics

Talevi

Bellera

2019

Expert Opinion on Drug Discovery

207

126

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Response to angiotensin blockade with irbesartan in a patient with metastatic colorectal cancer

Cited by 40 publications

References 27 publications

Genomic profiling of pelvic genital type leiomyosarcoma in a woman with a germlineCHEK2:c.1100delC mutation and a concomitant diagnosis of metastatic invasive ductal breast carcinoma

Genomic profiling of pelvic genital type leiomyosarcoma in a woman with a germlineCHEK2:c.1100delC mutation and a concomitant diagnosis of metastatic invasive ductal breast carcinoma

Identification of key pathways and genes changes in pancreatic cancer cells (BXPC-3) after cross-talk with primary pancreatic stellate cells using bioinformatics analysis

Challenges and opportunities with drug repurposing: finding strategies to find alternative uses of therapeutics

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