.

Molecular Oncology and Ovarian Pathologies

Reiner A. VEITIA

Our team focuses on the study of ovarian development and function through molecular genetics. Our research is carried out through the molecular analysis of different pathologies such as the blepharophimosis syndrome, premature ovarian insufficiency (POI) or granulosa cell tumors, affecting one of the somatic cell types of the ovary. One of the historical topics of the group is the analysis of the blepharophimosis syndrome, involving craniofacial anomalies and POI, due to alterations in the transcription factor (TF) FOXL2. Over the years, we have contributed to a better understanding of its molecular function, pathogenic mechanisms, targets and partners. We use FOXL2 as a model to explore the basis of the specific recognition of a target by a TF and the influence of partners and post-translational modifications in this process. We are also investigating the involvement of FOXL2 in adult granulosa cell tumors (AGCT). Indeed, a recurrent somatic mutation in FOXL2, leading to the p.C134W substitution has been detected in more than 97% of AGCTs, suggesting that this mutation is a key element (driver) in their formation. We are actively studying the pathogenic mechanisms of this mutation using CRISPR-Cas9 modified cell lines, an animal model and genomic tools. For the juvenile form of GCTs, we have recently reported the presence of insertions in the AKT1 oncogene that are likely responsible for the tumors, paving the way for further research. Finally, we are taking advantage of the power of current genomic technology to perform exome sequencing in familial and isolated cases of POI to uncover genes whose mutations are responsible for this condition. We have thus shown the involvement in POI of genes such as STAG3 or more recently MEIOB.

Keywords: Ovary, transcription factor, gene regulation, omics analysis, IOP, cancer

+33 (0)157278116     reiner.veitia(at)ijm.fr

The main objective of the research carried out by our team is the study of ovarian function through molecular genetics. A historical subject of the group has been the analysis of the Blepharophimosis syndrome (craniofacial anomalies and premature ovarian insufficiency or POI), due to alterations in the transcription factor FOXL2. Over the years, we have contributed to a better understanding of the molecular function of FOXL2, its mechanisms of pathogenicity and the discovery of numerous targets and partners. FOXL2 provides an excellent model to study the combinatorial regulation of transcription, as it modulates a series of apparently unrelated processes (e.g. cholesterol and steroid metabolism, apoptosis, cell cycle, free radical detoxification, etc.). Thus, we use FOXL2 as a model to explore the basis of specific target recognition by a transcription factor and the influence of its partners and post-translational modifications on this process. To do so, we use state-of-the-art genomics and proteomics tools.

 

Caption: FOXL2 interactome: protein-protein interaction network for 255 FOXL2 partners identified by co-immunoprecipitation and mass spectrometry.

 

FOXL2 has also opened an avenue of research into ovarian granulosa cell tumors (GCTs), which account for up to 8% of all ovarian cancers. Two distinct subtypes of GCTs have been described: juvenile and adult forms. The adult type occurs most often during perimenopause and is characterized by late recurrence (up to 40 years after treatment of the primary tumor). The juvenile form (JGCT) tends to occur in the prepubertal period. A recurrent somatic mutation in FOXL2, leading to the p.C134W substitution has been detected in more than 97% of AGCTs, suggesting that this mutation is a driver of their formation. We are actively investigating the pathogenic mechanisms of this mutation using CRISPR-Cas9 modified cell lines, an animal model and genomic tools.

The molecular basis of JGCT is less well understood. We recently found tandem duplications in the reading frame of the AKT1 oncogene that affect the pleckstrin-homology domain (PHD) of the protein in over 60% of JGCTs. The effects of these mutations are currently being studied in cell and Drosophila models.

 

        

Caption: HeLa cells expressing the normal version of AKT1 (right) and one of the mutated versions found in ovarian tumors (left) (core: blue, AKT1: red).

 

Finally, we are taking advantage of the power of current genomic technology to discover new genes involved in female infertility due to POI, by performing exome sequencing in familial and isolated cases of this disorder. The functions of candidate genes discovered in these analyses are or will be studied using molecular approaches and animal models.

Group leader:

Reiner VEITIA
Téléphone : +33 (0)157278116
Email : reiner.veitia (at) ijm.fr

 

Members:

Sandrine CABURET Researcher
Bérangère LEGOIS Biological technician
Anne-Laure TODESCHINI Researcher
Alain ZIDER Researcher

Reply to “An alternative miRISC targets a cancer-associated coding sequence mutation in FOXL2”. Veitia RA, Pilsworth J, Todeschini AL, Huntsman D.EMBO J. 2021 Aug 16;40(16):e107517. doi: 10.15252/embj.2020107517.PMID: 34396573

FOXL2 in adult-type granulosa cell tumour of the ovary: oncogene or tumour suppressor gene? Pilsworth JA, Todeschini AL, Neilson SJ, Cochrane DR, Lai D, Anttonen M, Heikinheimo M, Huntsman DG, Veitia RA.J Pathol. 2021 Nov;255(3):225-231. doi: 10.1002/path.5771. Epub 2021 Sep 1.PMID: 34338304

Insights into the pathogenicity of missense variants in the forkhead domain of FOX proteins underlying Mendelian disorders. Bermúdez-Guzmán L, Veitia RA. Hum Genet. 2021 Jul;140(7):999-1010.


Forkhead Transcription Factors in Health and Disease.
 Herman L, Todeschini AL, Veitia RA.Trends Genet. 2021 May;37(5):460-475 (Review).

Genomic exploration of the targets of FOXL2 and ESR2 unveils their implication in cell migration, invasion, and adhesion. Herman L, Legois B, Todeschini ALVeitia RA.FASEB J. 2021 Apr;35(4):e21355. doi: 10.1096/fj.202002444R.PMID: 33749886

A missense in HSF2BP causing primary ovarian insufficiency affects meiotic recombination by its novel interactor C19ORF57/BRME1. Felipe-Medina N, Caburet S, Sánchez-Sáez F, Condezo YB, de Rooij DG, Gómez-H L, Garcia-Valiente R, Todeschini AL, Duque P, Sánchez-Martin MA, Shalev SA, Llano E, Veitia RA, Pendás AM.Elife. 2020 Aug 26;9:e56996. doi: 10.7554/eLife.56996.PMID: 32845237 Free

An exome-wide exploration of cases of primary ovarian insufficiency uncovers novel sequence variants and candidate genes. Alvarez-Mora MI, Todeschini ALCaburet S, Perets LP, Mila M, Younis JS, Shalev S, Veitia RA.Clin Genet. 2020 Sep;98(3):293-298. doi: 10.1111/cge.13803. Epub 2020 Jul 28.PMID: 32613604

DHH pathogenic variants involved in 46,XY disorders of sex development differentially impact protein self-cleavage and structural conformation. Elzaiat M, Flatters D, Sierra-Díaz DC, Legois B, Laissue P, Veitia RA.Hum Genet. 2020 Nov;139(11):1455-1470.

Conventional and unconventional interactions of the transcription factor FOXL2 uncovered by a proteome-wide analysis. Penrad-Mobayed M, Perrin C, Herman L, Todeschini AL, Nigon F, Cosson B, Caburet SVeitia RA.FASEB J. 2020 Jan;34(1):571-587. doi: 10.1096/fj.201901573R. Epub 2019 Nov 25.PMID: 31914586


A truncating MEIOB mutation responsible for familial primary ovarian insufficiency abolishes its interaction with its partner SPATA22 and their recruitment to DNA double-strand breaks.
Caburet STodeschini AL, Petrillo C, Martini E, Farran ND, Legois B, Livera G, Younis JS, Shalev S, Veitia RA.EBioMedicine. 2019 Apr;42:524-531. doi: 10.1016/j.ebiom.2019.03.075. Epub 2019 Apr 15.PMID: 31000419

 

Veitia RA. Who ever thought genetic mutations were random? Trends Plant Sci. 2022 Mar 17:S1360-1385(22)00056-5. doi: 10.1016/j.tplants.2022.03.003. PMID: 35307269

Barakizou H, Gannouni S, Kamoun T, Mehdi M, Amary F, Huma Z, Todeschini AL, Veitia R, Donaldson M. Precocious Pseudo-puberty in a Two-year-old Girl, Presenting with Bilateral Ovarian Enlargement and Progressing to Unilateral Juvenile Granulosa Cell Tumour. J Clin Res Pediatr Endocrinol. 2022 Mar 3;14(1):107-113. doi: 10.4274/jcrpe.galenos.2021.2021.0039. Epub 2021 Apr 14. PMID: 33849266 Free PMC article.

Veitia RA, Innan H. Pathogenic “germline” variants associated with myeloproliferative disorders in apparently normal individuals: Inherited or acquired genetic alterations? Clin Genet. 2022 Mar;101(3):371-374. doi: 10.1111/cge.14104. Epub 2022 Jan 3. PMID: 34958119

Veitia RA, Birchler JA. Gene-dosage issues: a recurrent theme in whole genome duplication events. Trends Genet. 2022 Jan;38(1):1-3. doi: 10.1016/j.tig.2021.06.006. Epub 2021 Jun 29. PMID: 34215425

Veitia RA, Pilsworth J, Todeschini AL, Huntsman D. Reply to “An alternative miRISC targets a cancer-associated coding sequence mutation in FOXL2”. EMBO J. 2021 Aug 16;40(16):e107517. doi: 10.15252/embj.2020107517. PMID: 34396573;
PMCID: PMC8365250.

Picolo F, Grandchamp A, Piégu B, Rolland AD, Veitia RA, Monget P. Genes Encoding Teleost Orthologs of Human Haploinsufficient and Monoallelically Expressed Genes Remain in Duplicate More Frequently Than the Whole Genome. Int J Genomics. 2021 Jul 29;2021:9028667. doi: 10.1155/2021/9028667. PMID: 34368340;
PMCID: PMC8346308.

Pilsworth JA, Todeschini AL, Neilson SJ, Cochrane DR, Lai D, Anttonen M, Heikinheimo M, Huntsman DG, Veitia RA. FOXL2 in adult-type granulosa cell tumour of the ovary: oncogene or tumour suppressor gene? J Pathol. 2021 Nov;255(3):225-231. doi: 10.1002/path.5771. Epub 2021 Sep 1. PMID: 34338304.

Veitia RA, Birchler JA. Gene-dosage issues: a recurrent theme in whole genome duplication events. Trends Genet. 2021 Jun 29:S0168-9525(21)00147-5. doi: 10.1016/j.tig.2021.06.006. Epub ahead of print. PMID: 34215425.

Barakizou H, Gannouni S, Kamoun T, Mehdi M, Amary F, Huma Z, Todeschini AL, Veitia R, Donaldson M. Precocious pseudo-puberty in a 2-year-old girl, presenting with bilateral ovarian enlargement and progressing to unilateral juvenile granulosa cell tumour. J Clin Res Pediatr Endocrinol. 2021 Apr 14. doi: 10.4274/jcrpe.galenos.2021.2020.0039. Epub ahead of print. PMID: 33849266.

Herman L, Legois B, Todeschini AL, Veitia RA. Genomic exploration of the targets of FOXL2 and ESR2 unveils their implication in cell migration, invasion, and adhesion. FASEB J. 2021 Apr;35(4):e21355. doi: 10.1096/fj.202002444R. PMID: 33749886.

Bermúdez-Guzmán L, Veitia RA. Insights into the pathogenicity of missense variants in the forkhead domain of FOX proteins underlying Mendelian disorders. Hum Genet. 2021 Jul;140(7):999-1010. doi: 10.1007/s00439-021-02267-2. Epub 2021 Feb 27. PMID: 33638707.

Innan H, Vaiman D, Veitia RA. Predictable increase in female reproductive window: A simple model connecting age of reproduction, menopause, and longevity. Bioessays. 2021 May;43(5):e2000233. doi: 10.1002/bies.202000233. Epub 2021 Feb 11. PMID: 33569823.

Veitia RA. A reply to: Longitudinal changes in the frequency of mosaic chromosome Y loss in peripheral blood cells of aging men varies profoundly between individuals. Eur J Hum Genet. 2021 Sep;29(9):1321-1322. doi: 10.1038/s41431-020-00801-w. Epub 2021 Jan 18. PMID: 33462397; PMCID: PMC8440669.

Veitia RA. Clinical Genetics paving the way to the future. Clin Genet. 2021 Feb;99(2):217-218. doi: 10.1111/cge.13899. Epub 2020 Dec 26. PMID: 33368166.

Herman L, Todeschini AL, Veitia RA. Forkhead Transcription Factors in Health and Disease. Trends Genet. 2021 May;37(5):460-475. doi: 10.1016/j.tig.2020.11.003. Epub 2020 Dec 7. PMID: 33303287.

Felipe-Medina N, Caburet S, Sánchez-Sáez F, Condezo YB, de Rooij DG, Gómez-H L, Garcia-Valiente R, Todeschini AL, Duque P, Sánchez-Martin MA, Shalev SA, Llano E, Veitia RA, Pendás AM. A missense in HSF2BP causing primary ovarian
insufficiency affects meiotic recombination by its novel interactor C19ORF57/BRME1. Elife. 2020 Aug 26;9:e56996. doi: 10.7554/eLife.56996. PMID: 32845237; PMCID: PMC7498267.

Alvarez-Mora MI, Todeschini AL, Caburet S, Perets LP, Mila M, Younis JS, Shalev S, Veitia RA. An exome-wide exploration of cases of primary ovarian insufficiency uncovers novel sequence variants and candidate genes. Clin Genet.
2020 Sep;98(3):293-298. doi: 10.1111/cge.13803. Epub 2020 Jul 28. PMID: 32613604.

Elzaiat M, Flatters D, Sierra-Díaz DC, Legois B, Laissue P, Veitia RA. DHH pathogenic variants involved in 46,XY disorders of sex development differentially impact protein self-cleavage and structural conformation. Hum Genet. 2020 Nov;139(11):1455-1470. doi: 10.1007/s00439-020-02189-5. Epub 2020 Jun 5. PMID: 32504121.

Caburet S, Heddar A, Dardillac E, Creux H, Lambert M, Messiaen S, Tourpin S, Livera G, Lopez BS, Misrahi M. Homozygous hypomorphic <i>BRCA2</i> variant in primary ovarian insufficiency without cancer or Fanconi anaemia trait. J Med Genet. 2020 Jun 1:jmedgenet-2019-106672. doi: 10.1136/jmedgenet-2019-106672. Epub ahead of print. PMID: 32482800.

Govindaraju DR, Innan H, Veitia RA. The Muller’s Ratchet and Aging. Trends Genet. 2020 Jun;36(6):395-402. doi: 10.1016/j.tig.2020.02.004. Epub 2020 Mar 18. PMID: 32396833.

Veitia RA. Primary ovarian insufficiency, meiosis and DNA repair. Biomed J. 2020 Apr;43(2):115-123. doi: 10.1016/j.bj.2020.03.005. Epub 2020 May 4. PMID: 32381463; PMCID: PMC7283561.

Shi X, Chen C, Yang H, Hou J, Ji T, Cheng J, Veitia RA, Birchler JA. The Gene Balance Hypothesis: Epigenetics and Dosage Effects in Plants. Methods Mol Biol. 2020;2093:161-171. doi: 10.1007/978-1-0716-0179-2_12. PMID: 32088896.

Benayoun BA, Veitia RA. Special issue on “Molecular genetics of aging and longevity”: a critical time in the field of geroscience. Hum Genet. 2020 Mar;139(3):275-276. doi: 10.1007/s00439-020-02125-7. PMID: 32052140; PMCID:
PMC7041886.

Penrad-Mobayed M, Perrin C, Herman L, Todeschini AL, Nigon F, Cosson B, Caburet S, Veitia RA. Conventional and unconventional interactions of the transcription factor FOXL2 uncovered by a proteome-wide analysis. FASEB J. 2020
Jan;34(1):571-587. doi: 10.1096/fj.201901573R. Epub 2019 Nov 25. PMID: 31914586.

Innan H, Veitia R, Govindaraju DR. Genetic and epigenetic Muller’s ratchet as a mechanism of frailty and morbidity during aging: a demographic genetic model. Hum Genet. 2020 Mar;139(3):409-420. doi: 10.1007/s00439-019-02067-9. Epub 2019 Nov 11. PMID: 31713020.

Veitia RA. MIRAGE Syndrome: Phenotypic Rescue by Somatic Mutation and Selection. Trends Mol Med. 2019 Nov;25(11):937-940. doi: 10.1016/j.molmed.2019.08.008. Epub 2019 Oct 14. PMID: 31624021.

Veitia RA. DNA Content, Cell Size, and Cell Senescence. Trends Biochem Sci. 2019 Aug;44(8):645-647. doi: 10.1016/j.tibs.2019.04.013. Epub 2019 May 31. PMID: 31160123.

Johnson AF, Nguyen HT, Veitia RA. Causes and effects of haploinsufficiency. Biol Rev Camb Philos Soc. 2019 Oct;94(5):1774-1785. doi: 10.1111/brv.12527. Epub 2019 May 31. PMID: 31149781.

Grassmann F; International AMD Genomics Consortium (IAMDGC), Weber BHF, Veitia RA. Insights into the loss of the Y chromosome with age in control individuals and in patients with age-related macular degeneration using
genotyping microarray data. Hum Genet. 2020 Mar;139(3):401-407. doi: 10.1007/s00439-019-02029-1. Epub 2019 May 27. PMID: 31134332.

Caburet S, Todeschini AL, Petrillo C, Martini E, Farran ND, Legois B, Livera G, Younis JS, Shalev S, Veitia RA. A truncating MEIOB mutation responsible for familial primary ovarian insufficiency abolishes its interaction with its
partner SPATA22 and their recruitment to DNA double-strand breaks. EBioMedicine. 2019 Apr;42:524-531. doi: 10.1016/j.ebiom.2019.03.075. Epub 2019 Apr 15. PMID: 31000419; PMCID: PMC6491878.

Elzaiat M, Herman L, Legois B, Léger T, Todeschini AL, Veitia RA. High- throughput Exploration of the Network Dependent on AKT1 in Mouse Ovarian Granulosa Cells. Mol Cell Proteomics. 2019 Jul;18(7):1307-1319. doi:
10.1074/mcp.RA119.0014613. Epub 2019 Apr 16. PMID: 30992313; PMCID: PMC6601207.

Birchler JA, Veitia RA. Genomic Balance and Speciation. Epigenet Insights. 2019 Mar 31;12:2516865719840291. doi: 10.1177/2516865719840291. PMID: 30968064; PMCID: PMC6444768.

Veitia RA. Darwinian selection within an individual or somatic selection: facts and models. J Mol Cell Biol. 2019 Aug 19;11(8):719-722. doi: 10.1093/jmcb/mjz014. PMID: 30806666; PMCID: PMC6788724.

Veitia RA. Further quantitative insights into the decrease of heteroplasmy of m.3243A>G with age in leukocytes. Clin Genet. 2019 Apr;95(4):542-543. doi: 10.1111/cge.13496. Epub 2019 Jan 28. PMID: 30690711.

Veitia RA. AFF3: a new player in maintaining XIST monoallelic expression. J Mol Cell Biol. 2019 Sep 19;11(9):723-724. doi: 10.1093/jmcb/mjy082. PMID: 30629198; PMCID: PMC6821381.

Veitia RA. On the loss of human sex chromosomes in lymphocytes with age: a quantitative treatment. Eur J Hum Genet. 2018 Dec;26(12):1875-1878. doi: 10.1038/s41431-018-0225-0. Epub 2018 Aug 10. PMID: 30097617; PMCID: PMC6244361.

Veitia RA. Dosage effects in morphogenetic gradients of transcription factors: insights from a simple mathematical model. J Genet. 2018 Jun;97(2):365-370. PMID: 29932055.

Penrad-Mobayed M, Perrin C, L’Hôte D, Contremoulins V, Lepesant JA, Boizet- Bonhoure B, Poulat F, Baudin X, Veitia RA. A role for SOX9 in post- transcriptional processes: insights from the amphibian oocyte. Sci Rep. 2018 May
8;8(1):7191. doi: 10.1038/s41598-018-25356-1. PMID: 29740094; PMCID: PMC5940923.

Huhtaniemi I, Hovatta O, La Marca A, Livera G, Monniaux D, Persani L, Heddar A, Jarzabek K, Laisk-Podar T, Salumets A, Tapanainen JS, Veitia RA, Visser JA, Wieacker P, Wolczynski S, Misrahi M. Advances in the Molecular Pathophysiology, Genetics, and Treatment of Primary Ovarian Insufficiency. Trends Endocrinol Metab. 2018 Jun;29(6):400-419. doi: 10.1016/j.tem.2018.03.010. Epub 2018 Apr 26. PMID: 29706485.

Veitia RA. How the most common mitochondrial DNA mutation (m.3243A>G) vanishes from leukocytes: a mathematical model. Hum Mol Genet. 2018 May 1;27(9):1565-1571. doi: 10.1093/hmg/ddy063. PMID: 29474538.

Bernard V, Villa C, Auguste A, Lamothe S, Guillou A, Martin A, Caburet S, Young J, Veitia RA, Binart N. Natural and molecular history of prolactinoma: insights from a <i>Prlr</i><sup>-/-</sup> mouse model. Oncotarget. 2017 Dec
27;9(5):6144-6155. doi: 10.18632/oncotarget.23713. PMID: 29464061; PMCID: PMC5814201.

Bottani S, Zabet NR, Wendel JF, Veitia RA. Gene Expression Dominance in Allopolyploids: Hypotheses and Models. Trends Plant Sci. 2018 May;23(5):393-402. doi: 10.1016/j.tplants.2018.01.002. Epub 2018 Feb 9. PMID: 29433919.

Ouimette JF, Rougeulle C, Veitia RA. Three-dimensional genome architecture in health and disease. Clin Genet. 2019 Feb;95(2):189-198. doi: 10.1111/cge.13219. Epub 2018 Mar 2. PMID: 29377081.

Fouquet B, Pawlikowska P, Caburet S, Guigon C, Mäkinen M, Tanner L, Hietala M, Urbanska K, Bellutti L, Legois B, Bessieres B, Gougeon A, Benachi A, Livera G, Rosselli F, Veitia RA, Misrahi M. A homozygous <i>FANCM</i> mutation
underlies a familial case of non-syndromic primary ovarian insufficiency. Elife. 2017 Dec 12;6:e30490. doi: 10.7554/eLife.30490. PMID: 29231814; PMCID: PMC5764568.

Veitia RA. Gene Duplicates: Agents of Fragility? – A Reply to Landry and Diss. Trends Genet. 2017 Oct;33(10):658-660. doi: 10.1016/j.tig.2017.07.013. Epub 2017 Aug 17. PMID: 28823576.

Veitia RA, Caburet S, Birchler JA. Mechanisms of Mendelian dominance. Clin Genet. 2018 Mar;93(3):419-428. doi: 10.1111/cge.13107. Epub 2017 Oct 26. PMID: 28755412.

Paris F, Flatters D, Caburet S, Legois B, Servant N, Lefebvre H, Sultan C, Veitia RA. A novel variant of DHH in a familial case of 46,XY disorder of sex development: Insights from molecular dynamics simulations. Clin Endocrinol
(Oxf). 2017 Nov;87(5):539-544. doi: 10.1111/cen.13420. Epub 2017 Aug 13. PMID: 28708305.

Carlosama C, Elzaiat M, Patiño LC, Mateus HE, Veitia RA, Laissue P. A homozygous donor splice-site mutation in the meiotic gene MSH4 causes primary ovarian insufficiency. Hum Mol Genet. 2017 Aug 15;26(16):3161-3166. doi:
10.1093/hmg/ddx199. PMID: 28541421.

Veitia RA. Gene Duplicates: Agents of Robustness or Fragility? Trends Genet. 2017 Jun;33(6):377-379. doi: 10.1016/j.tig.2017.03.006. Epub 2017 Apr 20. PMID: 28434610.

Caburet S, Fruchter RB, Legois B, Fellous M, Shalev S, Veitia RA. A homozygous mutation of <i>GNRHR</i> in a familial case diagnosed with polycystic ovary syndrome. Eur J Endocrinol. 2017 May;176(5):K9-K14. doi: 10.1530/EJE-16-0968. PMID: 28348023.

Veitia RA, Govindaraju DR, Bottani S, Birchler JA. Aging: Somatic Mutations, Epigenetic Drift and Gene Dosage Imbalance. Trends Cell Biol. 2017 Apr;27(4):299-310. doi: 10.1016/j.tcb.2016.11.006. Epub 2016 Dec 9. PMID: 27939088.

Veitia RA. A Fresh Look at ‘Aging’ Proteins. Trends Biochem Sci. 2017 Feb;42(2):86-89. doi: 10.1016/j.tibs.2016.11.001. Epub 2016 Nov 14. PMID: 27856135.

Laissue P, Lakhal B, Vatin M, Batista F, Burgio G, Mercier E, Santos ED, Buffat C, Sierra-Diaz DC, Renault G, Montagutelli X, Salmon J, Monget P, Veitia RA, Méhats C, Fellous M, Gris JC, Cocquet J, Vaiman D. Association of FOXD1
variants with adverse pregnancy outcomes in mice and humans. Open Biol. 2016 Oct;6(10):160109. doi: 10.1098/rsob.160109. PMID: 27805902; PMCID: PMC5090055.

Elzaiat M, Todeschini AL, Caburet S, Veitia RA. The genetic make-up of ovarian development and function: the focus on the transcription factor FOXL2. Clin Genet. 2017 Feb;91(2):173-182. doi: 10.1111/cge.12862. Epub 2016 Sep 29. PMID: 27604691.

Bouilly J, Beau I, Barraud S, Bernard V, Azibi K, Fagart J, Fèvre A, Todeschini AL, Veitia RA, Beldjord C, Delemer B, Dodé C, Young J, Binart N. Identification of Multiple Gene Mutations Accounts for a new Genetic Architecture of Primary Ovarian Insufficiency. J Clin Endocrinol Metab. 2016 Dec;101(12):4541-4550. doi: 10.1210/jc.2016-2152. Epub 2016 Sep 7. PMID: 27603904.

Baetens D, Stoop H, Peelman F, Todeschini AL, Rosseel T, Coppieters F, Veitia RA, Looijenga LH, De Baere E, Cools M. NR5A1 is a novel disease gene for 46,XX testicular and ovotesticular disorders of sex development. Genet Med. 2017
Apr;19(4):367-376. doi: 10.1038/gim.2016.118. Epub 2016 Aug 4. PMID: 27490115; PMCID: PMC5392598.

Bottani S, Veitia RA. Hill function-based models of transcriptional switches: impact of specific, nonspecific, functional and nonfunctional binding. Biol Rev Camb Philos Soc. 2017 May;92(2):953-963. doi: 10.1111/brv.12262. Epub
2016 Apr 8. PMID: 27061969.

Birchler JA, Johnson AF, Veitia RA. Kinetics genetics: Incorporating the concept of genomic balance into an understanding of quantitative traits. Plant Sci. 2016 Apr;245:128-34. doi: 10.1016/j.plantsci.2016.02.002. Epub 2016 Feb 6. PMID: 26940497.

Fauchereau F, Shalev S, Chervinsky E, Beck-Fruchter R, Legois B, Fellous M, Caburet S, Veitia RA. A non-sense MCM9 mutation in a familial case of primary ovarian insufficiency. Clin Genet. 2016 May;89(5):603-7. doi: 10.1111/cge.12736.
Epub 2016 Feb 10. PMID: 26771056.

Veitia RA. Clinical Genetics in the age of Genomics and Genome editing. Clin Genet. 2016 Jan;89(1):3-4. doi: 10.1111/cge.12689. PMID: 26768808.

Auguste A, Bessière L, Todeschini AL, Caburet S, Sarnacki S, Prat J, D’angelo E, De La Grange P, Ariste O, Lemoine F, Legois B, Sultan C, Zider A, Galmiche L, Kalfa N, Veitia RA. Molecular analyses of juvenile granulosa cell tumors bearing AKT1 mutations provide insights into tumor biology and therapeutic leads. Hum Mol Genet. 2015 Dec 1;24(23):6687-98. doi: 10.1093/hmg/ddv373. Epub 2015 Sep 11. PMID: 26362254.

Coppieters F, Todeschini AL, Fujimaki T, Baert A, De Bruyne M, Van Cauwenbergh C, Verdin H, Bauwens M, Ongenaert M, Kondo M, Meire F, Murakami A, Veitia RA, Leroy BP, De Baere E. Hidden Genetic Variation in LCA9-Associated Congenital Blindness Explained by 5’UTR Mutations and Copy-Number Variations of NMNAT1. Hum Mutat. 2015 Dec;36(12):1188-96. doi: 10.1002/humu.22899. Epub 2015 Oct 1. PMID: 26316326; PMCID: PMC5054839.

Veitia RA, Birchler JA. Models of buffering of dosage imbalances in protein complexes. Biol Direct. 2015 Aug 15;10:42. doi: 10.1186/s13062-015-0063-8. PMID: 26275824; PMCID: PMC4537584.

Bessière L, Todeschini AL, Auguste A, Sarnacki S, Flatters D, Legois B, Sultan C, Kalfa N, Galmiche L, Veitia RA. A Hot-spot of In-frame Duplications Activates the Oncoprotein AKT1 in Juvenile Granulosa Cell Tumors. EBioMedicine.
2015 Mar 6;2(5):421-31. doi: 10.1016/j.ebiom.2015.03.002. PMID: 26137586; PMCID: PMC4485906.

Veitia RA, Potier MC. Gene dosage imbalances: action, reaction, and models. Trends Biochem Sci. 2015 Jun;40(6):309-17. doi: 10.1016/j.tibs.2015.03.011. Epub 2015 Apr 27. PMID: 25937627.

Petitjean M, Badel A, Veitia RA, Vanet A. Synthetic lethals in HIV: ways to avoid drug resistance : Running title: Preventing HIV resistance. Biol Direct. 2015 Apr 17;10:17. doi: 10.1186/s13062-015-0044-y. PMID: 25888435; PMCID:
PMC4399722.

Caburet S, Anttonen M, Todeschini AL, Unkila-Kallio L, Mestivier D, Butzow R, Veitia RA. Combined comparative genomic hybridization and transcriptomic analyses of ovarian granulosa cell tumors point to novel candidate driver genes.
BMC Cancer. 2015 Apr 10;15:251. doi: 10.1186/s12885-015-1283-0. PMID: 25884336; PMCID: PMC4407711.

Caburet S, Vilain É. Mutation de STAG3 – Une nouvelle cause d’insuffisance ovarienne prématurée [STAG3 in premature ovarian failure]. Med Sci (Paris). 2015 Feb;31(2):129-31. French. doi: 10.1051/medsci/20153102005. Epub 2015 Mar 4. PMID: 25744256.

Veitia RA, Veyrunes F, Bottani S, Birchler JA. X chromosome inactivation and active X upregulation in therian mammals: facts, questions, and hypotheses. J Mol Cell Biol. 2015 Feb;7(1):2-11. doi: 10.1093/jmcb/mjv001. Epub 2015 Jan 6. PMID: 25564545.

2016-2020 : Laëtitia Herman, thesis defense: 22/09/2020 « Caractérisation moléculaire du rôle de FOXL2 et de ses partenaires dans l’ovaire sain et pathologique »

2012-2015 : Laurianne Bessière, thesis defense: 16/09/2015 « Exploration génomique et fonctionnelle des tumeurs des cellules de la granulosa ovarienne »

2009-2013 : Adrien Georges, thesis defense: 28/06/2013 « FOXL2 : un déterminant de la signalisation dans l’ovaire »

2007-2011 : Bérénice Benayoun, thesis defense: 28/01/2011 « FOXL2 : un facteur de transcription essentiel de l’ovaire, à l’interface entre la réponse au stress cellulaire et la suppression tumorale »

2006-2009 : Aurélie Dipiétromaria, thesis defense: 28/09/2009 « Etudes des conséquences fonctionnelles des mutations de FOXL2 : gène impliqué dans le syndrome du BPES »

2005-2008 : Franck Batista Pelaez, thesis defense: 13/06/2008 « Les cibles transcriptionnelles de FOXL2, un facteur de transcription impliqué dans le développement et le maintien de la fonction ovarienne »

2005-2008 : Lara Moumné, thesis defense: 14/05/2008 « Etude fonctionnelle des mutations affectant FOXL2 : un acteur clé du développement de l’ovaire chez les vertébrés »

2002-2006 : Julie Cocquet thesis defense: 2006 « Evolution, expression et structure de FOXL2, un gène impliqué dans la fertilité féminine »

Studies on adult ovarian granulosa cell tumours (AGCTs) and the FOXL2 transcription factor: Team of E. de Baere, Ghent Belgium. Team of N. Binart, Kremlin-Bicêtre, France. F. Poulat, Montpellier, France. Team of M. Anttonen, Helsinki, Finland. Team D. Huntsman, Vancouver, Canada. Team of Alberto Pendas, Salamanca, Spain.

Studies on juvenile ovarian granulosa cell tumours (JGCTs) and the AKT1 oncoprotein: S. Sarnacki and L. Galmiche, Paris. N. Kalfa and C. Sultan, Montpellier. J. Prat and E. d’Angelo, Barcelona, Spain. Malcolm Donaldson, Glasgow, United Kingdom.

Studies on genes involved in premature ovarian failure: Maria Isabel Alvarez-Mora and Montserrat Mila, Barcelona, Spain. Gabriel Livera’s team, Fontenay aux Roses, France. Johnny S. Younis, Safed, Israel. Team of Stavit Shalev, Afula, Israel. Alberto Pendas’ team, Salamanca, Spain.

Translated with www.DeepL.com/Translator (free version)

1) ANR (National Agency for Research) : OVARYPROTECT : Interaction entre la signalisation PKA et TRIM28 dans la maintenance et la pathologie ovarienne

2) GEFLUC (Groupement des Entreprises Françaises dans la Lutte contre le Cancer): Ovarian cancer: FOXL2-C134W impact on cell-cell or cell-ECM adhesion.

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