Metabolomics signatures of a subset of RET variants according to their oncogenic risk level.

Abstract:

:Thirty percent of medullary thyroid carcinomas (MTCs) are related to dominant germline pathogenic variants in the RET proto-oncogene. According to their aggressiveness, these pathogenic variants are classified in three risk levels: 'moderate', 'high' and 'highest'. The present study compares the metabolomics profiles of five pathogenic variants, whether already classified or not. We have generated six stable murine fibroblast cell lines (NIH3T3) expressing the WT allele or variants of the human RET gene, with different levels of pathogenicity, including the M918V variant that is yet to be accurately classified. We carried out a targeted metabolomics study of the cell extracts with a QTRAP mass spectrometer, using the Biocrates Absolute IDQ p180 kit, which allows the quantification of 188 endogenous molecules. The data were then subjected to multivariate statistical analysis. One hundred seventy three metabolites were accurately measured. The metabolic profiles of the cells expressing the RET variants were found to be correlated with their oncogenic risk. In addition, the statistical model we constructed for predicting the oncogenic risk attributed a moderate risk to the M918V variant. Our results indicate that metabolomics may be useful for characterizing the pathogenicity of the RET gene variants and their levels of aggressiveness.

journal_name

Endocr Relat Cancer

journal_title

Endocrine-related cancer

authors

Veyrat-Durebex C,Bouzamondo N,Le Mao M,Chao de la Barca JM,Bris C,Dieu X,Simard G,Gadras C,Tessier L,Drui D,Borson-Chazot F,Barlier A,Reynier P,Prunier-Mirebeau D

doi

10.1530/ERC-18-0314

subject

Has Abstract

pub_date

2019-03-01 00:00:00

pages

379-389

issue

3

eissn

1351-0088

issn

1479-6821

pii

ERC-18-0314

journal_volume

26

pub_type

杂志文章
  • Prospective evaluation of estrogen receptor-beta in predicting response to neoadjuvant antiestrogen therapy in elderly breast cancer patients.

    abstract::It has been proposed that knowledge of estrogen receptor beta (ER-beta) expression may refine estrogen receptor alpha (ER-alpha) predictivity of response to endocrine therapy. We challenged this hypothesis in ER-alpha-positive breast cancers subjected to preoperative antiestrogen treatment. Forty-seven elderly (> or =...

    journal_title:Endocrine-related cancer

    pub_type: 临床试验,杂志文章

    doi:10.1677/erc.1.00822

    authors: Cappelletti V,Celio L,Bajetta E,Allevi A,Longarini R,Miodini P,Villa R,Fabbri A,Mariani L,Giovanazzi R,Galante E,Greco M,Grazia Daidone M

    更新日期:2004-12-01 00:00:00

  • Role of hypoxia-inducible factor-1alpha as a cancer therapy target.

    abstract::Hypoxia occurs in solid tumours due to a mismatch between tumour growth and angiogenesis. Hypoxia in solid tumours is associated with an aggressive phenotype and resistance to radiation therapy and chemotherapy leading to poor patient prognosis. Hypoxia-inducible factor-1 (HIF-1) is a transcription factor, which is ac...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章,评审

    doi:10.1677/erc.1.01290

    authors: Patiar S,Harris AL

    更新日期:2006-12-01 00:00:00

  • DUSP6/MKP3 is overexpressed in papillary and poorly differentiated thyroid carcinoma and contributes to neoplastic properties of thyroid cancer cells.

    abstract::Thyroid carcinomas derived from follicular cells comprise papillary thyroid carcinoma (PTC), follicular thyroid carcinoma, poorly differentiated thyroid carcinoma (PDTC) and undifferentiated anaplastic thyroid carcinoma (ATC). PTC, the most frequent thyroid carcinoma histotype, is associated with gene rearrangements t...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章

    doi:10.1530/ERC-12-0078

    authors: Degl'Innocenti D,Romeo P,Tarantino E,Sensi M,Cassinelli G,Catalano V,Lanzi C,Perrone F,Pilotti S,Seregni E,Pierotti MA,Greco A,Borrello MG

    更新日期:2013-01-21 00:00:00

  • Uncontrolled insulin secretion from a childhood pancreatic beta-cell adenoma is not due to the functional loss of ATP-sensitive potassium channels.

    abstract::We report the case of an 8-year-old child who presented with severe hyperinsulinaemic hypoglycaemia due to a pancreatic islet cell adenoma. In vivo, there was no beneficial response to the hyperglycaemia-inducing agent diazoxide and as a consequence the child underwent a subtotal pancreatectomy. In vitro studies of ad...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章

    doi:10.1677/erc.0.0090221

    authors: Hussain K,Cosgrove KE,Shepherd RM,Chapman JC,Swift SM,Smith VV,Kassem SA,Glaser B,Lindley KJ,Aynsley-Green A,Dunne MJ

    更新日期:2002-12-01 00:00:00

  • The LRIG family: enigmatic regulators of growth factor receptor signaling.

    abstract::The leucine-rich repeats and immunoglobulin-like domains (LRIG) family of transmembrane proteins contains three vertebrate members (LRIG1, LRIG2 and LRIG3) and one member each in flies (Lambik) and worms (Sma-10). LRIGs have stepped into the spotlight as essential regulators of growth factor receptors, including recep...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章,评审

    doi:10.1530/ERC-14-0179

    authors: Simion C,Cedano-Prieto ME,Sweeney C

    更新日期:2014-01-01 00:00:00

  • In vitro model systems to study androgen receptor signaling in prostate cancer.

    abstract::Prostate cancer (PCa) is one of the most common causes of male cancer-related death in Western nations. The cellular response to androgens is mediated via the androgen receptor (AR), a ligand-inducible transcription factor whose dysregulation plays a key role during PCa development and progression following androgen d...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章,评审

    doi:10.1530/ERC-12-0401

    authors: Sampson N,Neuwirt H,Puhr M,Klocker H,Eder IE

    更新日期:2013-03-26 00:00:00

  • PRKACB variants in skeletal disease or adrenocortical hyperplasia: effects on protein kinase A.

    abstract::Genetic variants in components of the protein kinase A (PKA) enzyme have been associated with various defects and neoplasms in the context of Carney complex (CNC) and in isolated cases, such as in primary pigmented nodular adrenocortical disease (PPNAD), cortisol-producing adrenal adenomas (CPAs), and various cancers....

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章

    doi:10.1530/ERC-20-0309

    authors: Espiard S,Drougat L,Settas N,Haydar S,Bathon K,London E,Levy I,Faucz FR,Calebiro D,Bertherat J,Li D,Levine MA,Stratakis CA

    更新日期:2020-11-01 00:00:00

  • Prognostic factors of papillary and follicular thyroid cancer: differences in an iodine-replete endemic goiter region.

    abstract::Papillary (PTC) and follicular thyroid carcinoma (FTC) are known as differentiated thyroid carcinoma (DTC). Nevertheless, according to the UICC/AJCC (TNM) classification PTC and FTC are frequently analyzed as one cancer. The aim of this study is to show differences in outcome and specific prognostic factors in an iodi...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章

    doi:10.1677/erc.0.0110131

    authors: Passler C,Scheuba C,Prager G,Kaczirek K,Kaserer K,Zettinig G,Niederle B

    更新日期:2004-03-01 00:00:00

  • Leptin deficiency suppresses MMTV-Wnt-1 mammary tumor growth in obese mice and abrogates tumor initiating cell survival.

    abstract::Obesity increases both the risk and mortality associated with many types of cancer including that of the breast. In mice, obesity increases both incidence of spontaneous tumors and burden of transplanted tumors. Our findings identify leptin, an adipose secreted cytokine, in promoting increased mammary tumor burden in ...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章

    doi:10.1530/ERC-11-0102

    authors: Zheng Q,Dunlap SM,Zhu J,Downs-Kelly E,Rich J,Hursting SD,Berger NA,Reizes O

    更新日期:2011-07-11 00:00:00

  • Prognostic factors of long-term outcome in gastroenteropancreatic neuroendocrine tumours.

    abstract::Neuroendocrine tumours (NET) of the gastroenteropancreatic system comprise a malignant entity with a low incidence. Only limited information is available on long-term clinical outcome and clinically applicable prognostic factors. We performed a retrospective analysis of a large, well-characterized centre-based patient...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章

    doi:10.1677/ERC-08-0017

    authors: Pape UF,Berndt U,Müller-Nordhorn J,Böhmig M,Roll S,Koch M,Willich SN,Wiedenmann B

    更新日期:2008-12-01 00:00:00

  • Is there an effect of ghrelin/ghrelin analogs on cancer? A systematic review.

    abstract::Ghrelin is a hormone with multiple physiologic functions, including promotion of growth hormone release, stimulation of appetite and regulation of energy homeostasis. Treatment with ghrelin/ghrelin-receptor agonists is a prospective therapy for disease-related cachexia and malnutrition. In vitro studies have shown hig...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章,评审

    doi:10.1530/ERC-16-0130

    authors: Sever S,White DL,Garcia JM

    更新日期:2016-09-01 00:00:00

  • CUX1: a modulator of tumour aggressiveness in pancreatic neuroendocrine neoplasms.

    abstract::Pancreatic neuroendocrine neoplasms (PNENs) constitute a rare tumour entity, and prognosis and treatment options depend on tumour-mediating hallmarks such as angiogenesis, proliferation rate and resistance to apoptosis. The molecular pathways that determine the malignant phenotype are still insufficiently understood a...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章

    doi:10.1530/ERC-14-0152

    authors: Krug S,Kühnemuth B,Griesmann H,Neesse A,Mühlberg L,Boch M,Kortenhaus J,Fendrich V,Wiese D,Sipos B,Friemel J,Gress TM,Michl P

    更新日期:2014-01-01 00:00:00

  • Role of chromosomal instability in cancer progression.

    abstract::Cancer cells often display chromosomal instability (CIN), a defect that involves loss or rearrangement of the cell's genetic material - chromosomes - during cell division. This process results in the generation of aneuploidy, a deviation from the haploid number of chromosomes, and structural alterations of chromosomes...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章,评审

    doi:10.1530/ERC-17-0187

    authors: McClelland SE

    更新日期:2017-09-01 00:00:00

  • Acquired resistance to aromatase inhibitors: where we stand!

    abstract::Aromatase inhibitors (AIs) are one of the principal therapeutic approaches for estrogen receptor-positive (ER+) breast cancer in postmenopausal women. They block estrogen biosynthesis through aromatase inhibition, thus preventing tumour progression. Besides the therapeutic success of the third-generation AIs, acquired...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章,评审

    doi:10.1530/ERC-17-0425

    authors: Augusto TV,Correia-da-Silva G,Rodrigues CMP,Teixeira N,Amaral C

    更新日期:2018-05-01 00:00:00

  • MicroRNA applications for prostate, ovarian and breast cancer in the era of precision medicine.

    abstract::The high degree of conservation in microRNA from Caenorhabditiselegans to humans has enabled relatively rapid implementation of findings in model systems to the clinic. The convergence of the capacity for genomic screening being implemented in the prevailing precision medicine initiative and the capabilities of microR...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章,评审

    doi:10.1530/ERC-16-0525

    authors: Smith B,Agarwal P,Bhowmick NA

    更新日期:2017-05-01 00:00:00

  • Pituitary tumors contain a side population with tumor stem cell-associated characteristics.

    abstract::Pituitary adenomas cause significant endocrine and mass-related morbidity. Little is known about the mechanisms that underlie pituitary tumor pathogenesis. In the present study, we searched for a side population (SP) in pituitary tumors representing cells with high efflux capacity and potentially enriched for tumor st...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章

    doi:10.1530/ERC-14-0546

    authors: Mertens F,Gremeaux L,Chen J,Fu Q,Willems C,Roose H,Govaere O,Roskams T,Cristina C,Becú-Villalobos D,Jorissen M,Poorten VV,Bex M,van Loon J,Vankelecom H

    更新日期:2015-08-01 00:00:00

  • Potentiated anti-tumor effects of BETi by MEKi in anaplastic thyroid cancer.

    abstract::Anaplastic thyroid cancer (ATC) is an aggressive malignancy with limited treatment options. We explored novel treatment modalities by targeting epigenetic modifications using inhibitors of BET (e.g. BRD4) activity. We evaluated the efficacy in the treatment of ATC of a novel BET inhibitor, PLX51107 (PLX), currently in...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章

    doi:10.1530/ERC-19-0107

    authors: Zhu X,Park S,Lee WK,Cheng SY

    更新日期:2019-09-01 00:00:00

  • The ubiquitin-proteasome system: opportunities for therapeutic intervention in solid tumors.

    abstract::The destruction of proteins via the ubiquitin-proteasome system is a multi-step, complex process involving polyubiquitination of substrate proteins, followed by proteolytic degradation by the macromolecular 26S proteasome complex. Inhibitors of the proteasome promote the accumulation of proteins that are deleterious t...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章,评审

    doi:10.1530/ERC-14-0005

    authors: Johnson DE

    更新日期:2015-02-01 00:00:00

  • Identification of a paired box gene 8-peroxisome proliferator-activated receptor gamma (PAX8-PPARgamma) rearrangement mosaicism in a patient with an autonomous functioning follicular thyroid carcinoma bearing an activating mutation in the TSH receptor.

    abstract::Our main objective was to search for mutations in candidate genes and for paired box gene 8-peroxisome proliferator-activated receptor gamma (PAX8-PPARgamma) rearrangement in a well-differentiated angioinvasive follicular thyroid carcinoma (FTC) causing hyperthyroidism. DNA and RNA were extracted from the patient's th...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章

    doi:10.1677/ERC-09-0069

    authors: Lado-Abeal J,Celestino R,Bravo SB,Garcia-Rendueles ME,de la Calzada J,Castro I,Castro P,Espadinha C,Palos F,Soares P,Alvarez CV,Sobrinho-Simões M,Cameselle-Teijeiro J

    更新日期:2010-06-03 00:00:00

  • The oestrogen metabolite 2-methoxyoestradiol alone or in combination with tumour necrosis factor-related apoptosis-inducing ligand mediates apoptosis in cancerous but not healthy cells of the human endometrium.

    abstract::Cancers of the reproductive tract account for 12% of all malignancies in women. As previous studies have shown that oestrogen metabolites can cause apoptosis, we characterised the effect of oestrogen and oestrogen metabolites on non-cancerous and cancerous human endometrial cells. Herein, we demonstrate that 2-methoxy...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章

    doi:10.1677/ERC-07-0008

    authors: Kato S,Sadarangani A,Lange S,Villalón M,Brañes J,Brosens JJ,Owen GI,Cuello M

    更新日期:2007-06-01 00:00:00

  • p300 is upregulated by docetaxel and is a target in chemoresistant prostate cancer.

    abstract::Administration of the microtubule inhibitor docetaxel is a common treatment for metastatic castration-resistant prostate cancer (mCRPC) and results in prolonged patient overall survival. Usually, after a short period of time chemotherapy resistance emerges and there is urgent need to find new therapeutic targets to ov...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章

    doi:10.1530/ERC-19-0488

    authors: Gruber M,Ferrone L,Puhr M,Santer FR,Furlan T,Eder IE,Sampson N,Schäfer G,Handle F,Culig Z

    更新日期:2020-03-01 00:00:00

  • Role of exon-16-deleted HER2 in breast carcinomas.

    abstract::A splice variant of the human gene HER2, lacking exon-16 (DeltaHER2) which encodes a small extracellular region, has been described. This altered receptor forms disulfide bond-stabilized homodimers. We report here that the DeltaHER2 splice variant represents about 9% of the HER2 mRNA obtained from most of the 46 breas...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章

    doi:10.1677/erc.1.01047

    authors: Castiglioni F,Tagliabue E,Campiglio M,Pupa SM,Balsari A,Ménard S

    更新日期:2006-03-01 00:00:00

  • Advances in paraganglioma-pheochromocytoma cell lines and xenografts.

    abstract::This review describes human and rodent-derived cell lines and xenografts developed over the last five decades that are suitable or potentially suitable models for paraganglioma-pheochromocytoma research. We outline the strengths and weaknesses of various models and emphasize the recurring theme that, despite the major...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章,评审

    doi:10.1530/ERC-19-0434

    authors: Bayley JP,Devilee P

    更新日期:2020-12-01 00:00:00

  • Tumour-associated fibroblasts contribute to neoangiogenesis in human parathyroid neoplasia.

    abstract::Components of the tumour microenvironment initiate and promote cancer development. In this study, we investigated the stromal component of parathyroid neoplasia. Immunohistochemistry for alpha-smooth muscle actin (α-SMA) showed an abundant periacinar distribution of α-SMA(+) cells in normal parathyroid glands (n=3). T...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章

    doi:10.1530/ERC-14-0161

    authors: Verdelli C,Avagliano L,Creo P,Guarnieri V,Scillitani A,Vicentini L,Steffano GB,Beretta E,Soldati L,Costa E,Spada A,Bulfamante GP,Corbetta S

    更新日期:2015-02-01 00:00:00

  • Human melanoma cells express functional receptors for thyroid-stimulating hormone.

    abstract::We have reported a high prevalence of hypothyroidism in the cutaneous melanoma population, suggesting that the pathologic hormonal environment of hypothyroidism promotes melanoma growth. The objective of this study was to test the hypothesis that TSH, which circulates at elevated levels in hypothyroid individuals, sti...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章

    doi:10.1677/erc.1.01239

    authors: Ellerhorst JA,Sendi-Naderi A,Johnson MK,Cooke CP,Dang SM,Diwan AH

    更新日期:2006-12-01 00:00:00

  • Loss of neuronatin expression is associated with promoter hypermethylation in pituitary adenoma.

    abstract::The imprinted gene, neuronatin (NNAT), is one of the most abundant transcripts in the pituitary and is thought to be involved in the development and maturation of this gland. In a recent whole-genome approach, exploiting a pituitary tumour cell line, we identified hypermethylation associated loss of NNAT. In this repo...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章

    doi:10.1677/ERC-09-0008

    authors: Revill K,Dudley KJ,Clayton RN,McNicol AM,Farrell WE

    更新日期:2009-06-01 00:00:00

  • Combining doxorubicin-nanobubbles and shockwaves for anaplastic thyroid cancer treatment: preclinical study in a xenograft mouse model.

    abstract::Anaplastic thyroid cancer is one of the most lethal diseases, and a curative therapy does not exist. Doxorubicin, the only drug approved for anaplastic thyroid cancer treatment, has a very low response rate and causes numerous side effects among which cardiotoxicity is the most prominent. Thus, doxorubicin delivery to...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章

    doi:10.1530/ERC-17-0045

    authors: Marano F,Frairia R,Rinella L,Argenziano M,Bussolati B,Grange C,Mastrocola R,Castellano I,Berta L,Cavalli R,Catalano MG

    更新日期:2017-06-01 00:00:00

  • The miR-200 family controls beta-tubulin III expression and is associated with paclitaxel-based treatment response and progression-free survival in ovarian cancer patients.

    abstract::Ovarian cancer remains one of the leading causes of cancer deaths. Thus, new biomarkers predictive of response to the standard paclitaxel-carboplatin treatment are needed to improve chemotherapy strategies. MicroRNAs have the potential to modify drug outcomes. Based on this, we have demonstrated in this study that pat...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章

    doi:10.1677/ERC-10-0148

    authors: Leskelä S,Leandro-García LJ,Mendiola M,Barriuso J,Inglada-Pérez L,Muñoz I,Martínez-Delgado B,Redondo A,de Santiago J,Robledo M,Hardisson D,Rodríguez-Antona C

    更新日期:2010-12-21 00:00:00

  • HEREDITARY ENDOCRINE TUMOURS: CURRENT STATE-OF-THE-ART AND RESEARCH OPPORTUNITIES: Early thyroidectomy in multiple endocrine neoplasia: a four decade experience.

    abstract::Forty years ago, physicians caring for the J-kindred, a 100+ member family with multiple endocrine neoplasia type 2A (MEN2A), hypothesized that early thyroidectomy based on measurement of the biomarker calcitonin could cure patients at risk for development of medullary thyroid carcinoma (MTC). We re-evaluated 22 famil...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章

    doi:10.1530/ERC-20-0108

    authors: Grubbs EG,Lechan RM,Edeiken-Monroe B,Cote GJ,Trotter C,Tischler AS,Gagel RF

    更新日期:2020-08-01 00:00:00

  • MAPK and SHH pathways modulate type 3 deiodinase expression in papillary thyroid carcinoma.

    abstract::Type 3 deiodinase (DIO3, D3) is reactivated in human neoplasias. Increased D3 levels in papillary thyroid carcinoma (PTC) have been associated with tumor size and metastatic disease. The objective of this study is to investigate the signaling pathways involved in DIO3 upregulation in PTC. Experiments were performed in...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章

    doi:10.1530/ERC-15-0162

    authors: Romitti M,Wajner SM,Ceolin L,Ferreira CV,Ribeiro RV,Rohenkohl HC,Weber Sde S,Lopez PL,Fuziwara CS,Kimura ET,Maia AL

    更新日期:2016-03-01 00:00:00