Specific Genomic Alterations in High-Grade Pulmonary Neuroendocrine Tumours with Carcinoid Morphology

2020 ◽  
Vol 111 (1-2) ◽  
pp. 158-169 ◽  
Author(s):  
Jerôme Cros ◽  
Nathalie Théou-Anton ◽  
Valérie Gounant ◽  
Remy Nicolle ◽  
Cécile Reyes ◽  
...  
Keyword(s):  
Neuroendocrine Tumours ◽  
Genetic Alterations ◽  
Copy Number Variations ◽  
Chromatin Remodelling ◽  
Tumour Suppressor ◽  
Tumour Suppressor Genes ◽  
High Grade ◽  
Ki 67 ◽  
Suppressor Genes ◽  
Genetic Landscape

<b><i>Introduction:</i></b> High-grade lung neuroendocrine tumours with carcinoid morphology have been recently reported; they may represent the thoracic counterparts of grade 3 digestive neuroendocrine tumours. We aimed to study their genetic landscape including analysis of tumoral heterogeneity. <b><i>Methods:</i></b> Eleven patients with high-grade (&#x3e;20% Ki-67 and/or &#x3e;10 mitoses) lung neuroendocrine tumours with a carcinoid morphology were included. We analysed copy number variations, somatic mutations, and protein expression in 16 tumour samples (2 samples were available for 5 patients allowing us to study spatial and temporal heterogeneity). <b><i>Results:</i></b> Genomic patterns were heterogeneous ranging from “quiet” to tetraploid, heavily rearranged genomes. Oncogene mutations were rare and most genetic alterations targeted tumour suppressor genes. Chromosomes 11 (7/11), 3 (6/11), 13 (4/11), and 6–17 (3/11) were the most frequently lost. Altered tumour suppressor genes were common to both carcinoids and neuroendocrine carcinomas, involving different pathways including chromatin remodelling (<i>KMT2A</i>, <i>ARID1A</i>, <i>SETD2</i>, <i>SMARCA2</i>, <i>BAP1</i>, <i>PBRM1</i>, <i>KAT6A</i>), DNA repair (<i>MEN1</i>, <i>POLQ</i>, <i>ATR</i>, <i>MLH1</i>, <i>ATM</i>), cell cycle (<i>RB1</i>, <i>TP53</i>, <i>CDKN2A</i>), cell adhesion (<i>LATS2</i>, <i>CTNNB1</i>, <i>GSK3B</i>) and metabolism (<i>VHL</i>). Comparative spatial/temporal analyses confirmed that these tumours emerged from clones of lower aggressivity but revealed that they were genetically heterogeneous accumulating “neuroendocrine carcinoma-like” genetic alterations through progression such as <i>TP53/RB1</i> alterations. <b><i>Conclusion:</i></b> These data confirm the importance of chromatin remodelling genes in pulmonary carcinoids and highlight the potential role of <i>TP53</i> and <i>RB1</i> to drive the transformation in more aggressive high-grade tumours.

scholarly journals Posttransplant Lymphoproliferative Disorders

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Hazem A. H. Ibrahim ◽  
Kikkeri N. Naresh
Keyword(s):  
Transplant Rejection ◽  
Subsequent Development ◽  
Genetic Alterations ◽  
Immunosuppressive Drugs ◽  
Lymphoproliferative Disorders ◽  
Tumour Suppressor ◽  
Antigenic Stimulation ◽  
Tumour Suppressor Genes ◽  
Suppressor Genes ◽  
Posttransplant Lymphoproliferative Disorders

Posttransplant lymphoproliferative disorders (PTLDs) are a group of diseases that range from benign polyclonal to malignant monoclonal lymphoid proliferations. They arise secondary to treatment with immunosuppressive drugs given to prevent transplant rejection. Three main pathologic subsets/stages of evolution are recognised: early, polymorphic, and monomorphic lesions. The pathogenesis of PTLDs seems to be multifactorial. Among possible infective aetiologies, the role of EBV has been studied in depth, and the virus is thought to play a central role in driving the proliferation of EBV-infected B cells that leads to subsequent development of the lymphoproliferative disorder. It is apparent, however, that EBV is not solely responsible for the “neoplastic” state. Accumulated genetic alterations of oncogenes and tumour suppressor genes (deletions, mutations, rearrangements, and amplifications) and epigenetic changes (aberrant hypermethylation) that involve tumour suppressor genes are integral to the pathogenesis. Antigenic stimulation also plays an evident role in the pathogenesis of PTLDs. Plasmacytoid dendritic cells (PDCs) that are critical to fight viral infections have been thought to play a pathogenetically relevant role in PTLDs. Furthermore, regulatory T cells (Treg cells), which are modulators of immune reactions once incited, seem to have an important role in PTLDs where antigenic stimulation is key for the pathogenesis.

scholarly journals Exclusion of BBC1 and CMAR as candidate breast tumour-suppressor genes

1997 ◽  
Vol 76 (12) ◽  
pp. 1550-1553 ◽  
Author(s):  
E Moerland ◽  
MH Breuning ◽  
CJ Cornelisse ◽  
AM Cleton-Jansen
Keyword(s):  
Breast Tumour ◽  
Tumour Suppressor ◽  
Tumour Suppressor Genes ◽  
Suppressor Genes

Infrequent loss of heterozygosity of the major tumour suppressor genes in Indian oral cancers

2002 ◽  
Vol 31 (4) ◽  
pp. 414-418 ◽  
Author(s):  
S. Kannan ◽  
H. Yokozaki ◽  
K. Jayasree ◽  
P. Sebastian ◽  
A. Mathews ◽  
...  
Keyword(s):  
Loss Of Heterozygosity ◽  
Tumour Suppressor ◽  
Tumour Suppressor Genes ◽  
Suppressor Genes ◽  
Oral Cancers

Tumour Suppressor Genes in Hodgkin’s Disease

1995 ◽  
pp. 209-222
Author(s):  
Miguel A. Piris ◽  
Juan C. Martinez ◽  
Margarita Sanchez-Beato ◽  
Juan F. Garcia ◽  
Carmen Bellas ◽  
...  
Keyword(s):  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Tumour Suppressor ◽  
Tumour Suppressor Genes ◽  
Suppressor Genes

scholarly journals Pan-cancer characterisation of microRNA with hallmarks of cancer reveals role of microRNA-mediated downregulation of tumour suppressor genes

2017 ◽  
Author(s):  
Andrew Dhawan ◽  
Jacob G. Scott ◽  
Adrian L. Harris ◽  
Francesca M. Buffa
Keyword(s):  
Penalized Regression ◽  
Tumour Suppressor ◽  
The Cancer Genome Atlas ◽  
Clinical Samples ◽  
Tumour Suppressor Genes ◽  
Alternative Mechanism ◽  
Mirna Regulation ◽  
Hallmarks Of Cancer ◽  
Suppressor Genes ◽  
Copy Number Changes

microRNA are key regulators of the human transcriptome across a number of diverse biological processes, such as development, aging, and cancer, where particular miRNA have been identified as tumour suppressive and oncogenic. In this work, we sought to elucidate, in a comprehensive manner, across 15 epithelial cancer types comprising 7,316 clinical samples from the Cancer Genome Atlas, the association of miRNA expression and target regulation with the pheno-typic hallmarks of cancer. Utilising penalized regression techniques to integrate transcriptomic, methylation and mutation data, we find evidence for a complex map of interactions underlying the relationship of miRNA regulation and the hallmarks of cancer. This highlighted high redundancy for the oncomiR-1 cluster of oncogenic miRNAs, in particular hsa-miR-17-5p. In addition, we reveal extensive miRNA regulation of tumour suppressor genes such as PTEN, FAT4, and CDK12, uncovering an alternative mechanism of repression in the absence of mutation, methylation or copy number changes.

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