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1. Dissecting the Origin of Heterogeneity in Uterine and Ovarian Carcinosarcomas

Author

Anne-Sophie Sertier, Anthony Ferrari, Roxane M. Pommier, Isabelle Treilleux, Sandrine Boyault, Mojgan Devouassoux-Shisheboran, Janice Kielbassa, Emilie Thomas, Laurie Tonon, Vincent Le Texier, Amandine Charreton, Anne-Pierre Morel, Anne Floquet, Florence Joly, Dominique Berton-Rigaud, Gwenaël Ferron, Laurent Arnould, Sabrina Croce, Guillaume Bataillon, Pierre Saintigny, Eliane Mery-Lamarche, Christine Sagan, Aruni P. Senaratne, Ivo G. Gut, Fabien Calvo, Alain Viari, Maria Ouzounova, Isabelle Ray-Coquard, and Alain Puisieux

Abstract

Gynecologic carcinosarcomas (CS) are biphasic neoplasms composed of carcinomatous (C) and sarcomatous (S) malignant components. Because of their rarity and histologic complexity, genetic and functional studies on CS are scarce and the mechanisms of initiation and development remain largely unknown. Whole-genome analysis of the C and S components reveals shared genomic alterations, thus emphasizing the clonal evolution of CS. Reconstructions of the evolutionary history of each tumor further reveal that C and S samples are composed of both ancestral cell populations and component-specific subclones, supporting a common origin followed by distinct evolutionary trajectories. However, while we do not find any recurrent genomic features associated with phenotypic divergence, transcriptomic and methylome analyses identify a common mechanism across the cohort, the epithelial-to-mesenchymal transition (EMT), suggesting a role for nongenetic factors in inflicting changes to cellular fate. Altogether, these data accredit the hypothesis that CS tumors are driven by both clonal evolution and transcriptomic reprogramming, essential for susceptibility to transdifferentiation upon encountering environmental cues, thus linking CS heterogeneity to genetic, transcriptomic, and epigenetic influences. Significance: We have provided a detailed characterization of the genomic landscape of CS and identified EMT as a common mechanism associated with phenotypic divergence, linking CS heterogeneity to genetic, transcriptomic, and epigenetic influences.

Published
2023

2. Figure S2 from Dissecting the Origin of Heterogeneity in Uterine and Ovarian Carcinosarcomas

Author

Alain Puisieux, Isabelle Ray-Coquard, Maria Ouzounova, Alain Viari, Fabien Calvo, Ivo G. Gut, Aruni P. Senaratne, Christine Sagan, Eliane Mery-Lamarche, Pierre Saintigny, Guillaume Bataillon, Sabrina Croce, Laurent Arnould, Gwenaël Ferron, Dominique Berton-Rigaud, Florence Joly, Anne Floquet, Anne-Pierre Morel, Amandine Charreton, Vincent Le Texier, Laurie Tonon, Emilie Thomas, Janice Kielbassa, Mojgan Devouassoux-Shisheboran, Sandrine Boyault, Isabelle Treilleux, Roxane M. Pommier, Anthony Ferrari, and Anne-Sophie Sertier

Abstract

Heterogeneity of genomic rearrangements in carcinosarcoma.

Published
2023

3. Figure S13 from Dissecting the Origin of Heterogeneity in Uterine and Ovarian Carcinosarcomas

Author

Alain Puisieux, Isabelle Ray-Coquard, Maria Ouzounova, Alain Viari, Fabien Calvo, Ivo G. Gut, Aruni P. Senaratne, Christine Sagan, Eliane Mery-Lamarche, Pierre Saintigny, Guillaume Bataillon, Sabrina Croce, Laurent Arnould, Gwenaël Ferron, Dominique Berton-Rigaud, Florence Joly, Anne Floquet, Anne-Pierre Morel, Amandine Charreton, Vincent Le Texier, Laurie Tonon, Emilie Thomas, Janice Kielbassa, Mojgan Devouassoux-Shisheboran, Sandrine Boyault, Isabelle Treilleux, Roxane M. Pommier, Anthony Ferrari, and Anne-Sophie Sertier

Abstract

Complete clonal evolution of P01 tumor.

Published
2023

4. Figure S5 from Dissecting the Origin of Heterogeneity in Uterine and Ovarian Carcinosarcomas

Author

Alain Puisieux, Isabelle Ray-Coquard, Maria Ouzounova, Alain Viari, Fabien Calvo, Ivo G. Gut, Aruni P. Senaratne, Christine Sagan, Eliane Mery-Lamarche, Pierre Saintigny, Guillaume Bataillon, Sabrina Croce, Laurent Arnould, Gwenaël Ferron, Dominique Berton-Rigaud, Florence Joly, Anne Floquet, Anne-Pierre Morel, Amandine Charreton, Vincent Le Texier, Laurie Tonon, Emilie Thomas, Janice Kielbassa, Mojgan Devouassoux-Shisheboran, Sandrine Boyault, Isabelle Treilleux, Roxane M. Pommier, Anthony Ferrari, and Anne-Sophie Sertier

Abstract

BRCAness feature: tandem duplicator phenotype.

Published
2023

5. Figure S12 from Dissecting the Origin of Heterogeneity in Uterine and Ovarian Carcinosarcomas

Author

Alain Puisieux, Isabelle Ray-Coquard, Maria Ouzounova, Alain Viari, Fabien Calvo, Ivo G. Gut, Aruni P. Senaratne, Christine Sagan, Eliane Mery-Lamarche, Pierre Saintigny, Guillaume Bataillon, Sabrina Croce, Laurent Arnould, Gwenaël Ferron, Dominique Berton-Rigaud, Florence Joly, Anne Floquet, Anne-Pierre Morel, Amandine Charreton, Vincent Le Texier, Laurie Tonon, Emilie Thomas, Janice Kielbassa, Mojgan Devouassoux-Shisheboran, Sandrine Boyault, Isabelle Treilleux, Roxane M. Pommier, Anthony Ferrari, and Anne-Sophie Sertier

Abstract

Complete clonal evolution of P02 tumor.

Published
2023

6. Figure S14 from Dissecting the Origin of Heterogeneity in Uterine and Ovarian Carcinosarcomas

Author

Alain Puisieux, Isabelle Ray-Coquard, Maria Ouzounova, Alain Viari, Fabien Calvo, Ivo G. Gut, Aruni P. Senaratne, Christine Sagan, Eliane Mery-Lamarche, Pierre Saintigny, Guillaume Bataillon, Sabrina Croce, Laurent Arnould, Gwenaël Ferron, Dominique Berton-Rigaud, Florence Joly, Anne Floquet, Anne-Pierre Morel, Amandine Charreton, Vincent Le Texier, Laurie Tonon, Emilie Thomas, Janice Kielbassa, Mojgan Devouassoux-Shisheboran, Sandrine Boyault, Isabelle Treilleux, Roxane M. Pommier, Anthony Ferrari, and Anne-Sophie Sertier

Abstract

Complete clonal evolution of P05 tumor.

Published
2023

7. Supplementary Table 1 from Dissecting the Origin of Heterogeneity in Uterine and Ovarian Carcinosarcomas

Author

Alain Puisieux, Isabelle Ray-Coquard, Maria Ouzounova, Alain Viari, Fabien Calvo, Ivo G. Gut, Aruni P. Senaratne, Christine Sagan, Eliane Mery-Lamarche, Pierre Saintigny, Guillaume Bataillon, Sabrina Croce, Laurent Arnould, Gwenaël Ferron, Dominique Berton-Rigaud, Florence Joly, Anne Floquet, Anne-Pierre Morel, Amandine Charreton, Vincent Le Texier, Laurie Tonon, Emilie Thomas, Janice Kielbassa, Mojgan Devouassoux-Shisheboran, Sandrine Boyault, Isabelle Treilleux, Roxane M. Pommier, Anthony Ferrari, and Anne-Sophie Sertier

Abstract

Curated list of chromatin remodeling genes.

Published
2023

8. Figure S16 from Dissecting the Origin of Heterogeneity in Uterine and Ovarian Carcinosarcomas

Author

Alain Puisieux, Isabelle Ray-Coquard, Maria Ouzounova, Alain Viari, Fabien Calvo, Ivo G. Gut, Aruni P. Senaratne, Christine Sagan, Eliane Mery-Lamarche, Pierre Saintigny, Guillaume Bataillon, Sabrina Croce, Laurent Arnould, Gwenaël Ferron, Dominique Berton-Rigaud, Florence Joly, Anne Floquet, Anne-Pierre Morel, Amandine Charreton, Vincent Le Texier, Laurie Tonon, Emilie Thomas, Janice Kielbassa, Mojgan Devouassoux-Shisheboran, Sandrine Boyault, Isabelle Treilleux, Roxane M. Pommier, Anthony Ferrari, and Anne-Sophie Sertier

Abstract

Complete clonal evolution of P15 tumor.

Published
2023

9. FIGURE 1 from Dissecting the Origin of Heterogeneity in Uterine and Ovarian Carcinosarcomas

Author

Alain Puisieux, Isabelle Ray-Coquard, Maria Ouzounova, Alain Viari, Fabien Calvo, Ivo G. Gut, Aruni P. Senaratne, Christine Sagan, Eliane Mery-Lamarche, Pierre Saintigny, Guillaume Bataillon, Sabrina Croce, Laurent Arnould, Gwenaël Ferron, Dominique Berton-Rigaud, Florence Joly, Anne Floquet, Anne-Pierre Morel, Amandine Charreton, Vincent Le Texier, Laurie Tonon, Emilie Thomas, Janice Kielbassa, Mojgan Devouassoux-Shisheboran, Sandrine Boyault, Isabelle Treilleux, Roxane M. Pommier, Anthony Ferrari, and Anne-Sophie Sertier

Abstract

Genomic landscape of CS. A, Tissue origin and histological subtypes for each tumor (from P01 to P15). B, Main component and detailed percentage content for both samples (a and b) derived from the same tumor. C, CNA analysis: tumor purity (%), ploidy, FGA, and CNA breakpoints number. D, SV number, classified as deletion, duplication, inversion, and interchromosomal translocation. E, SNV and small indel number. F, Proportion of each of four mutational signatures deciphered in the whole cohort. G, MSI phenotype: MSI score (representing the percentage of unstable microsatellite loci), MLH1 promoter methylation (beta-value), and mRNA expression level (TPM – transcripts per million). H, Kataegis number illustrating APOBEC error-prone DNA repair process. I, BRCAness phenotype: number of LST, (white stars highlight samples with LST number ≥20), BRCA1 promoter methylation level (beta-value), BRCA1/2 genes alterations and TDP score, collectively summarized by the HRD status track.

Published
2023

10. Supplementary Table 3 from Dissecting the Origin of Heterogeneity in Uterine and Ovarian Carcinosarcomas

Author

Alain Puisieux, Isabelle Ray-Coquard, Maria Ouzounova, Alain Viari, Fabien Calvo, Ivo G. Gut, Aruni P. Senaratne, Christine Sagan, Eliane Mery-Lamarche, Pierre Saintigny, Guillaume Bataillon, Sabrina Croce, Laurent Arnould, Gwenaël Ferron, Dominique Berton-Rigaud, Florence Joly, Anne Floquet, Anne-Pierre Morel, Amandine Charreton, Vincent Le Texier, Laurie Tonon, Emilie Thomas, Janice Kielbassa, Mojgan Devouassoux-Shisheboran, Sandrine Boyault, Isabelle Treilleux, Roxane M. Pommier, Anthony Ferrari, and Anne-Sophie Sertier

Abstract

List of differentially methylated gene promoters (paired analysis of 5 selected tumors).

Published
2023

11. Figure S7 from Dissecting the Origin of Heterogeneity in Uterine and Ovarian Carcinosarcomas

Author

Alain Puisieux, Isabelle Ray-Coquard, Maria Ouzounova, Alain Viari, Fabien Calvo, Ivo G. Gut, Aruni P. Senaratne, Christine Sagan, Eliane Mery-Lamarche, Pierre Saintigny, Guillaume Bataillon, Sabrina Croce, Laurent Arnould, Gwenaël Ferron, Dominique Berton-Rigaud, Florence Joly, Anne Floquet, Anne-Pierre Morel, Amandine Charreton, Vincent Le Texier, Laurie Tonon, Emilie Thomas, Janice Kielbassa, Mojgan Devouassoux-Shisheboran, Sandrine Boyault, Isabelle Treilleux, Roxane M. Pommier, Anthony Ferrari, and Anne-Sophie Sertier

Abstract

Alteration of chromatin remodeling genes in uterine and ovarian CS.

Published
2023

12. Figure S1 from Dissecting the Origin of Heterogeneity in Uterine and Ovarian Carcinosarcomas

Author

Alain Puisieux, Isabelle Ray-Coquard, Maria Ouzounova, Alain Viari, Fabien Calvo, Ivo G. Gut, Aruni P. Senaratne, Christine Sagan, Eliane Mery-Lamarche, Pierre Saintigny, Guillaume Bataillon, Sabrina Croce, Laurent Arnould, Gwenaël Ferron, Dominique Berton-Rigaud, Florence Joly, Anne Floquet, Anne-Pierre Morel, Amandine Charreton, Vincent Le Texier, Laurie Tonon, Emilie Thomas, Janice Kielbassa, Mojgan Devouassoux-Shisheboran, Sandrine Boyault, Isabelle Treilleux, Roxane M. Pommier, Anthony Ferrari, and Anne-Sophie Sertier

Abstract

Collection and selection of tumor samples.

Published
2023

13. FIGURE 2 from Dissecting the Origin of Heterogeneity in Uterine and Ovarian Carcinosarcomas

Author

Alain Puisieux, Isabelle Ray-Coquard, Maria Ouzounova, Alain Viari, Fabien Calvo, Ivo G. Gut, Aruni P. Senaratne, Christine Sagan, Eliane Mery-Lamarche, Pierre Saintigny, Guillaume Bataillon, Sabrina Croce, Laurent Arnould, Gwenaël Ferron, Dominique Berton-Rigaud, Florence Joly, Anne Floquet, Anne-Pierre Morel, Amandine Charreton, Vincent Le Texier, Laurie Tonon, Emilie Thomas, Janice Kielbassa, Mojgan Devouassoux-Shisheboran, Sandrine Boyault, Isabelle Treilleux, Roxane M. Pommier, Anthony Ferrari, and Anne-Sophie Sertier

Abstract

Key gene alterations in uterine and ovarian CS. Oncoprint of alterations identified in the 50 most altered genes from TCGA cancer pathways and custom lists of CRG. The type of genomic alteration (deletion, amplification, fusion, broken by SV, missense, truncated) is described in the legend. Number and proportions of alteration types are summarized by gene (horizontal bars on right) and by sample (vertical bars on top). The samples are classified into MSI and CN-high according to TCGA endometrial carcinoma classification.

Published
2023

14. Figure S15 from Dissecting the Origin of Heterogeneity in Uterine and Ovarian Carcinosarcomas

Author

Alain Puisieux, Isabelle Ray-Coquard, Maria Ouzounova, Alain Viari, Fabien Calvo, Ivo G. Gut, Aruni P. Senaratne, Christine Sagan, Eliane Mery-Lamarche, Pierre Saintigny, Guillaume Bataillon, Sabrina Croce, Laurent Arnould, Gwenaël Ferron, Dominique Berton-Rigaud, Florence Joly, Anne Floquet, Anne-Pierre Morel, Amandine Charreton, Vincent Le Texier, Laurie Tonon, Emilie Thomas, Janice Kielbassa, Mojgan Devouassoux-Shisheboran, Sandrine Boyault, Isabelle Treilleux, Roxane M. Pommier, Anthony Ferrari, and Anne-Sophie Sertier

Abstract

Complete clonal evolution of P12 tumor.

Published
2023

15. FIGURE 4 from Dissecting the Origin of Heterogeneity in Uterine and Ovarian Carcinosarcomas

Author

Alain Puisieux, Isabelle Ray-Coquard, Maria Ouzounova, Alain Viari, Fabien Calvo, Ivo G. Gut, Aruni P. Senaratne, Christine Sagan, Eliane Mery-Lamarche, Pierre Saintigny, Guillaume Bataillon, Sabrina Croce, Laurent Arnould, Gwenaël Ferron, Dominique Berton-Rigaud, Florence Joly, Anne Floquet, Anne-Pierre Morel, Amandine Charreton, Vincent Le Texier, Laurie Tonon, Emilie Thomas, Janice Kielbassa, Mojgan Devouassoux-Shisheboran, Sandrine Boyault, Isabelle Treilleux, Roxane M. Pommier, Anthony Ferrari, and Anne-Sophie Sertier

Abstract

Evolutionary histories of CS. Clonal lineage histories of P02 MSI phenotype tumor (A), P12 BRCAness-phenotype tumor (B), and P15 ovarian bilateral tumor (C). Left, Clonal lineage inference for the whole tumor: subclonal populations (Ci), main cancer gene alterations, genome doubling events, and representative mutational signature proportions are represented. Right, Subclonal population frequencies projection in each tumor sample. Clones colored in gray are found in both derived samples, pink (or green) clones are specific to sarcoma- (or carcinoma-) derived samples, respectively.

Published
2023

16. FIGURE 3 from Dissecting the Origin of Heterogeneity in Uterine and Ovarian Carcinosarcomas

Author

Alain Puisieux, Isabelle Ray-Coquard, Maria Ouzounova, Alain Viari, Fabien Calvo, Ivo G. Gut, Aruni P. Senaratne, Christine Sagan, Eliane Mery-Lamarche, Pierre Saintigny, Guillaume Bataillon, Sabrina Croce, Laurent Arnould, Gwenaël Ferron, Dominique Berton-Rigaud, Florence Joly, Anne Floquet, Anne-Pierre Morel, Amandine Charreton, Vincent Le Texier, Laurie Tonon, Emilie Thomas, Janice Kielbassa, Mojgan Devouassoux-Shisheboran, Sandrine Boyault, Isabelle Treilleux, Roxane M. Pommier, Anthony Ferrari, and Anne-Sophie Sertier

Abstract

Differential expression and methylation analysis (C vs. S). A, Heatmap and pathway overrepresentation analysis of differentially expressed genes between C and S (or undifferentiated) components of the 10 samples derived from the five selected CS tumors. Gene clustering method: Ward's; distance: Spearman. FDR: false discovery rate. B, Heatmaps of EMT and stemness pathways scores (left) and methylation level of EMT-related miRNAs (right). mRNA level: scaled TPM. Pathway scores: scaled ssGSEA scores. Methylation level: scaled beta-values.

Published
2023

17. Supplementary Table 2 from Dissecting the Origin of Heterogeneity in Uterine and Ovarian Carcinosarcomas

Author

Alain Puisieux, Isabelle Ray-Coquard, Maria Ouzounova, Alain Viari, Fabien Calvo, Ivo G. Gut, Aruni P. Senaratne, Christine Sagan, Eliane Mery-Lamarche, Pierre Saintigny, Guillaume Bataillon, Sabrina Croce, Laurent Arnould, Gwenaël Ferron, Dominique Berton-Rigaud, Florence Joly, Anne Floquet, Anne-Pierre Morel, Amandine Charreton, Vincent Le Texier, Laurie Tonon, Emilie Thomas, Janice Kielbassa, Mojgan Devouassoux-Shisheboran, Sandrine Boyault, Isabelle Treilleux, Roxane M. Pommier, Anthony Ferrari, and Anne-Sophie Sertier

Abstract

List of differentially expressed genes (paired analysis of 5 selected tumors).

Published
2023

18. Figure S11 from Dissecting the origin of heterogeneity in uterine and ovarian carcinosarcomas

Author

Alain Puisieux, Isabelle Ray-Coquard, Maria Ouzounova, Alain Viari, Fabien Calvo, Ivo G. Gut, Aruni P. Senaratne, Christine Sagan, Eliane Mery-Lamarche, Pierre Saintigny, Guillaume Bataillon, Sabrina Croce, Laurent Arnould, Gwenaël Ferron, Dominique Berton-Rigaud, Florence Joly, Anne Floquet, Anne-Pierre Morel, Amandine Charreton, Vincent Le Texier, Laurie Tonon, Emilie Thomas, Janice Kielbassa, Mojgan Devouassoux-Shisheboran, Sandrine Boyault, Isabelle Treilleux, Roxane M. Pommier, Anthony Ferrari, and Anne-Sophie Sertier

Abstract

Differential methylation analysis (C vs S).

Published
2023

19. Figure S9 from Dissecting the origin of heterogeneity in uterine and ovarian carcinosarcomas

Author

Alain Puisieux, Isabelle Ray-Coquard, Maria Ouzounova, Alain Viari, Fabien Calvo, Ivo G. Gut, Aruni P. Senaratne, Christine Sagan, Eliane Mery-Lamarche, Pierre Saintigny, Guillaume Bataillon, Sabrina Croce, Laurent Arnould, Gwenaël Ferron, Dominique Berton-Rigaud, Florence Joly, Anne Floquet, Anne-Pierre Morel, Amandine Charreton, Vincent Le Texier, Laurie Tonon, Emilie Thomas, Janice Kielbassa, Mojgan Devouassoux-Shisheboran, Sandrine Boyault, Isabelle Treilleux, Roxane M. Pommier, Anthony Ferrari, and Anne-Sophie Sertier

Abstract

Clustering of somatic copy number alterations profiles.

Published
2023

20. Figure S4 from Dissecting the origin of heterogeneity in uterine and ovarian carcinosarcomas

Author

Alain Puisieux, Isabelle Ray-Coquard, Maria Ouzounova, Alain Viari, Fabien Calvo, Ivo G. Gut, Aruni P. Senaratne, Christine Sagan, Eliane Mery-Lamarche, Pierre Saintigny, Guillaume Bataillon, Sabrina Croce, Laurent Arnould, Gwenaël Ferron, Dominique Berton-Rigaud, Florence Joly, Anne Floquet, Anne-Pierre Morel, Amandine Charreton, Vincent Le Texier, Laurie Tonon, Emilie Thomas, Janice Kielbassa, Mojgan Devouassoux-Shisheboran, Sandrine Boyault, Isabelle Treilleux, Roxane M. Pommier, Anthony Ferrari, and Anne-Sophie Sertier

Abstract

APOBEC-related kataegis event.

Published
2023

21. Figure S10 from Dissecting the origin of heterogeneity in uterine and ovarian carcinosarcomas

Author

Alain Puisieux, Isabelle Ray-Coquard, Maria Ouzounova, Alain Viari, Fabien Calvo, Ivo G. Gut, Aruni P. Senaratne, Christine Sagan, Eliane Mery-Lamarche, Pierre Saintigny, Guillaume Bataillon, Sabrina Croce, Laurent Arnould, Gwenaël Ferron, Dominique Berton-Rigaud, Florence Joly, Anne Floquet, Anne-Pierre Morel, Amandine Charreton, Vincent Le Texier, Laurie Tonon, Emilie Thomas, Janice Kielbassa, Mojgan Devouassoux-Shisheboran, Sandrine Boyault, Isabelle Treilleux, Roxane M. Pommier, Anthony Ferrari, and Anne-Sophie Sertier

Abstract

Analysis of common genomic events between paired tumor samples.

Published
2023

22. Figure S3 from Dissecting the origin of heterogeneity in uterine and ovarian carcinosarcomas

Author

Alain Puisieux, Isabelle Ray-Coquard, Maria Ouzounova, Alain Viari, Fabien Calvo, Ivo G. Gut, Aruni P. Senaratne, Christine Sagan, Eliane Mery-Lamarche, Pierre Saintigny, Guillaume Bataillon, Sabrina Croce, Laurent Arnould, Gwenaël Ferron, Dominique Berton-Rigaud, Florence Joly, Anne Floquet, Anne-Pierre Morel, Amandine Charreton, Vincent Le Texier, Laurie Tonon, Emilie Thomas, Janice Kielbassa, Mojgan Devouassoux-Shisheboran, Sandrine Boyault, Isabelle Treilleux, Roxane M. Pommier, Anthony Ferrari, and Anne-Sophie Sertier

Abstract

Clustering of CS mutational signatures with COSMIC signatures.

Published
2023

23. Figure S8 from Dissecting the origin of heterogeneity in uterine and ovarian carcinosarcomas

Author

Alain Puisieux, Isabelle Ray-Coquard, Maria Ouzounova, Alain Viari, Fabien Calvo, Ivo G. Gut, Aruni P. Senaratne, Christine Sagan, Eliane Mery-Lamarche, Pierre Saintigny, Guillaume Bataillon, Sabrina Croce, Laurent Arnould, Gwenaël Ferron, Dominique Berton-Rigaud, Florence Joly, Anne Floquet, Anne-Pierre Morel, Amandine Charreton, Vincent Le Texier, Laurie Tonon, Emilie Thomas, Janice Kielbassa, Mojgan Devouassoux-Shisheboran, Sandrine Boyault, Isabelle Treilleux, Roxane M. Pommier, Anthony Ferrari, and Anne-Sophie Sertier

Abstract

Alteration of genes of RAS pathway in uterine and ovarian CS.

Published
2023

24. Supplementary Tables 1-2, Figures 1-5 from Regulation of Insulin-like Growth Factor–Mammalian Target of Rapamycin Signaling by MicroRNA in Childhood Adrenocortical Tumors

Author

Enzo Lalli, Gerard P. Zambetti, Bonald C. Figueiredo, Maria Helena C. Peralta-Del Valle, Wei Zhao, Jinling Wang, Emilie Thomas, Bruno Cardinaud, Abeer El Wakil, and Mabrouka Doghman

Abstract

Supplementary Tables 1-2, Figures 1-5 from Regulation of Insulin-like Growth Factor–Mammalian Target of Rapamycin Signaling by MicroRNA in Childhood Adrenocortical Tumors

Published
2023

25. Supplementary Table 1 from Regulation of Insulin-like Growth Factor–Mammalian Target of Rapamycin Signaling by MicroRNA in Childhood Adrenocortical Tumors

Author

Enzo Lalli, Gerard P. Zambetti, Bonald C. Figueiredo, Maria Helena C. Peralta-Del Valle, Wei Zhao, Jinling Wang, Emilie Thomas, Bruno Cardinaud, Abeer El Wakil, and Mabrouka Doghman

Abstract

Supplementary Table 1 from Regulation of Insulin-like Growth Factor–Mammalian Target of Rapamycin Signaling by MicroRNA in Childhood Adrenocortical Tumors

Published
2023

26. Data from Regulation of Insulin-like Growth Factor–Mammalian Target of Rapamycin Signaling by MicroRNA in Childhood Adrenocortical Tumors

Author

Enzo Lalli, Gerard P. Zambetti, Bonald C. Figueiredo, Maria Helena C. Peralta-Del Valle, Wei Zhao, Jinling Wang, Emilie Thomas, Bruno Cardinaud, Abeer El Wakil, and Mabrouka Doghman

Abstract

MicroRNAs (miRNAs) act at the posttranscriptional level to control gene expression in virtually every biological process, including oncogenesis. Here, we report the identification of a set of miRNAs that are differentially regulated in childhood adrenocortical tumors (ACT), including miR-99a and miR-100. Functional analysis of these miRNAs in ACT cell lines showed that they coordinately regulate expression of the insulin-like growth factor–mammalian target of rapamycin (mTOR)–raptor signaling pathway through binding sites in their 3′-untranslated regions. In these cells, the active Ser2448-phosphorylated form of mTOR is present only in mitotic cells in association with the mitotic spindle and midbody in the G2-M phases of the cell cycle. Pharmacologic inhibition of mTOR signaling by everolimus greatly reduces tumor cell growth in vitro and in vivo. Our results reveal a novel mechanism of regulation of mTOR signaling by miRNAs, and they lay the groundwork for clinical evaluation of drugs inhibiting the mTOR pathway for treatment of adrenocortical cancer. Cancer Res; 70(11); 4666–75. ©2010 AACR.

Published
2023

27. A Genome-Wide Association Study (GWAS) of Event-Free Survival (EFS) in Follicular Lymphoma Patients Treated with Front-Line Immunochemotherapy: A Lysa, Iowa/Mayo MER, and FIL Study

Author

Herve Ghesquieres, Youenn Drouet, Susan L. Slager, Franck Morschhauser, Sara Galimberti, Dennis P. Robinson, Emilie Thomas, Anne J. Novak, Luc Xerri, Stefano Luminari, Aurelie Verney, Camille Laurent, Lisa M. Rimsza, Thomas M. Habermann, Massimo Federico, Brian K. Link, Gilles Salles, and James R. Cerhan

Subjects
Immunology, Cell Biology, Hematology, Biochemistry
Published
2022

28. Verbal memory formation across PET-based Braak stages of tau accumulation in Alzheimer’s disease

Author

Jaime Fernández Arias, Joseph Therriault, Emilie Thomas, Firoza Z Lussier, Gleb Bezgin, Cécile Tissot, Stijn Servaes, Sulantha S Mathotaarachchi, Dorothée Schoemaker, Jenna Stevenson, Nesrine Rahmouni, Min Su Kang, Vanessa Pallen, Nina Margherita Poltronetti, Yi-Ting Wang, Peter Kunach, Mira Chamoun, Kely M Quispialaya S, Paolo Vitali, Gassan Massarweh, Serge Gauthier, Maria N Rajah, Tharick Pascoal, and Pedro Rosa-Neto

Subjects
Cellular and Molecular Neuroscience, Psychiatry and Mental health, Neurology, Biological Psychiatry
Abstract

A classical early sign of typical Alzheimer’s disease is memory decline, which has been linked to the aggregation of tau in the medial temporal lobe. Verbal delayed free recall and recognition tests have consistently probed useful to detect early memory decline, and there is substantial debate on how performance, particularly in recognition tests, is differentially affected through health and disease in older adults. Using in vivo PET-Braak staging, we investigated delayed recall and recognition memory dysfunction across the Alzheimer’s disease spectrum. Our cross-sectional study included 144 cognitively unimpaired elderly, 39 amyloid-β+ individuals with mild cognitive impairment and 29 amyloid-β+ Alzheimer’s disease patients from the Translational Biomarkers in Aging and Dementia cohort, who underwent [18F]MK6240 tau and [18F]AZD4694 amyloid PET imaging, structural MRI and memory assessments. We applied non-parametric comparisons, correlation analyses, regression models and voxel-wise analyses. In comparison with PET-Braak Stage 0, we found that reduced, but not clinically significant, delayed recall starts at PET-Braak Stage II (adjusted P < 0.0015), and that recognition (adjusted P = 0.011) displayed a significant decline starting at PET-Braak Stage IV. While performance in both delayed recall and recognition related to tau in nearly the same cortical areas, further analyses showed that delayed recall rendered stronger associations in areas of early tau accumulation, whereas recognition displayed stronger correlations in mostly posterior neocortical regions. Our results support the notion that delayed recall and recognition deficits are predominantly associated with tau load in allocortical and neocortical areas, respectively. Overall, delayed recall seems to be more dependent on the integrity of anterior medial temporal lobe structures, while recognition appears to be more affected by tau accumulation in cortices beyond medial temporal regions.

Published
2023

29. Author Correction: [11C]Martinostat PET analysis reveals reduced HDAC I availability in Alzheimer’s disease

Author

Tharick A. Pascoal, Mira Chamoun, Elad Lax, Hsiao-Ying Wey, Monica Shin, Kok Pin Ng, Min Su Kang, Sulantha Mathotaarachchi, Andrea L. Benedet, Joseph Therriault, Firoza Z. Lussier, Frederick A. Schroeder, Jonathan M. DuBois, Baileigh G. Hightower, Tonya M. Gilbert, Nicole R. Zürcher, Changning Wang, Robert Hopewell, Mallar Chakravarty, Melissa Savard, Emilie Thomas, Sara Mohaddes, Sarah Farzin, Alyssa Salaciak, Stephanie Tullo, A. Claudio Cuello, Jean-Paul Soucy, Gassan Massarweh, Heungsun Hwang, Eliane Kobayashi, Bradley T. Hyman, Bradford C. Dickerson, Marie-Christine Guiot, Moshe Szyf, Serge Gauthier, Jacob M. Hooker, and Pedro Rosa-Neto

Subjects
Multidisciplinary, General Physics and Astronomy, General Chemistry, General Biochemistry, Genetics and Molecular Biology
Published
2022

30. [11C]Martinostat PET analysis reveals reduced HDAC I availability in Alzheimer’s disease

Author

Tharick A. Pascoal, Mira Chamoun, Elad Lax, Hsiao-Ying Wey, Monica Shin, Kok Pin Ng, Min Su Kang, Sulantha Mathotaarachchi, Andrea L. Benedet, Joseph Therriault, Firoza Z. Lussier, Frederick A. Schroeder, Jonathan M. DuBois, Baileigh G. Hightower, Tonya M. Gilbert, Nicole R. Zürcher, Changning Wang, Robert Hopewell, Mallar Chakravarty, Melissa Savard, Emilie Thomas, Sara Mohaddes, Sarah Farzin, Alyssa Salaciak, Stephanie Tullo, A. Claudio Cuello, Jean-Paul Soucy, Gassan Massarweh, Heungsun Hwang, Eliane Kobayashi, Bradley T. Hyman, Bradford C. Dickerson, Marie-Christine Guiot, Moshe Szyf, Serge Gauthier, Jacob M. Hooker, and Pedro Rosa-Neto

Subjects
Multidisciplinary, General Physics and Astronomy, General Chemistry, General Biochemistry, Genetics and Molecular Biology
Abstract

Alzheimer’s disease (AD) is characterized by the brain accumulation of amyloid-β and tau proteins. A growing body of literature suggests that epigenetic dysregulations play a role in the interplay of hallmark proteinopathies with neurodegeneration and cognitive impairment. Here, we aim to characterize an epigenetic dysregulation associated with the brain deposition of amyloid-β and tau proteins. Using positron emission tomography (PET) tracers selective for amyloid-β, tau, and class I histone deacetylase (HDAC I isoforms 1–3), we find that HDAC I levels are reduced in patients with AD. HDAC I PET reduction is associated with elevated amyloid-β PET and tau PET concentrations. Notably, HDAC I reduction mediates the deleterious effects of amyloid-β and tau on brain atrophy and cognitive impairment. HDAC I PET reduction is associated with 2-year longitudinal neurodegeneration and cognitive decline. We also find HDAC I reduction in the postmortem brain tissue of patients with AD and in a transgenic rat model expressing human amyloid-β plus tau pathology in the same brain regions identified in vivo using PET. These observations highlight HDAC I reduction as an element associated with AD pathophysiology.

Published
2022

31. The Rice

Author

Hinda, Doucouré, Florence, Auguy, Servane, Blanvillain-Baufumé, Sandrine, Fabre, Marc, Gabriel, Emilie, Thomas, Fleur, Dambreville, Coline, Sciallano, Boris, Szurek, Ousmane, Koita, Valérie, Verdier, and Sébastien, Cunnac

Subjects
Plant Breeding, Xanthomonas, Bacterial Proteins, Gene Expression Regulation, Plant, Talc, Oryza, Disease Susceptibility, Transcription Activator-Like Effectors, Disease Resistance, Plant Diseases, Plant Proteins
Published
2022

32. Topographic Distribution of Amyloid-β, Tau, and Atrophy in Patients With Behavioral/Dysexecutive Alzheimer Disease

Author

Tatsuhiro Terada, Cecile Tissot, Joseph Therriault, Andrea Lessa Benedet, Soham Rej, Firoza Z. Lussier, Emilie Thomas, Jean-Paul Soucy, Serge Gauthier, Ziad S. Nasreddine, Mira Chamoun, Paramita Saha-Chaudhuri, Gassan Massarweh, Tharick A. Pascoal, Paolo Vitali, Melissa Savard, Pedro Rosa-Neto, and Min Su Kang

Subjects
Male, 0301 basic medicine, Amyloid β, Neuroimaging, tau Proteins, computer.software_genre, Article, 03 medical and health sciences, 0302 clinical medicine, Atrophy, Alzheimer Disease, Voxel, medicine, Humans, Distribution (pharmacology), Aged, Amyloid beta-Peptides, Receiver operating characteristic, business.industry, Mental Disorders, Memory clinic, Brain, Middle Aged, medicine.disease, Phenotype, 030104 developmental biology, Female, Neurology (clinical), Alzheimer's disease, business, Neuroscience, computer, 030217 neurology & neurosurgery, Executive dysfunction
Abstract

ObjectiveTo determine the associations between amyloid-PET, tau-PET, and atrophy with the behavioral/dysexecutive presentation of Alzheimer disease (AD), how these differ from amnestic AD, and how they correlate to clinical symptoms.MethodsWe assessed 15 patients with behavioral/dysexecutive AD recruited from a tertiary care memory clinic, all of whom had biologically defined AD. They were compared with 25 patients with disease severity– and age-matched amnestic AD and a group of 131 cognitively unimpaired (CU) elderly individuals. All participants were evaluated with amyloid-PET with [18F]AZD4694, tau-PET with [18F]MK6240, MRI, and neuropsychological testing.ResultsVoxelwise contrasts identified patterns of frontal cortical tau aggregation in behavioral/dysexecutive AD, with peaks in medial prefrontal, anterior cingulate, and frontal insular cortices in contrast to amnestic AD. No differences were observed in the distribution of amyloid-PET or atrophy as determined by voxel-based morphometry. Voxelwise area under the receiver operating characteristic curve analyses revealed that tau-PET uptake in the medial prefrontal, anterior cingulate, and frontal insular cortices were best able to differentiate between behavioral/dysexecutive and amnestic AD (area under the curve 0.87). Voxelwise regressions demonstrated relationships between frontal cortical tau load and degree of executive dysfunction.ConclusionsOur results provide evidence of frontal cortical involvement of tau pathology in behavioral/dysexecutive AD and highlight the need for consensus clinical criteria in this syndrome.

Published
2020

33. An atypical class of non-coding small RNAs produced in rice leaves upon bacterial infection

Author

Coline Sciallano, Alvaro L. Perez Quintero, Christophe Brugidou, Boris Szurek, Sébastien Cunnac, Aurore Comte, Emilie Thomas, Lisa Claude, Jonathan M. Jacobs, Séverine Lacombe, Ganna Reshetnyak, Adam J. Bogdanove, Anne Dievart, Clemence Medina, Ralf Koebnik, and Florence Auguy

Subjects
Genetics, Oryza sativa, Xanthomonas oryzae, Protein kinase domain, Transfer RNA, food and beverages, Gene silencing, Coding region, Virulence, Biology, biology.organism_classification, Type three secretion system
Abstract

Non-coding small RNAs (sRNA) act as mediators of gene silencing and regulate plant growth, development and stress responses. Early insights into plant sRNAs established a role in antiviral defense and they are now extensively studied across plant-microbe interactions. Here, sRNA sequencing discovered a class of sRNA in rice (Oryza sativa) specifically associated with foliar diseases caused by Xanthomonas oryzae bacteria. Xanthomonas-induced small RNAs (xisRNAs) loci were distinctively upregulated in response to diverse virulent strains at an early stage of infection producing a single duplex of 20-22nt sRNAs. xisRNAs production was dependent on the Type III secretion system, a major bacterial virulence factor for host colonization. xisRNA loci overlap with annotated transcripts sequences often encoding protein kinase domain proteins. A number of the corresponding rice cis-genes have documented functions in immune signaling and some xisRNA loci coincide with the coding sequence of a conserved kinase motif. xisRNAs exhibit features of small interfering RNAs and their biosynthesis depend on canonical components OsDCL1 and OsHEN1. xisRNA induction possibly mediates post-transcriptional gene silencing but they do not broadly suppress cis-genes expression on the basis of mRNA-seq data. Overall, our results identify a group of unusual sRNAs with a potential role in plant-microbe interactions.

Published
2021

34. Microglial sex dimorphism poses greater vulnerability to Alzheimer’s disease in females: A cross‐species study

Author

Emilie Thomas, Tatsuhiro Terada, Sulantha Mathotaarachchi, Arturo Aliaga, Yi-Ting Wang, Melissa Savard, Nesrine Rahmouni, Gassan Massarweh, Cecile Tissot, Firoza Z. Lussier, Jaime Fernandez Arias, Min Su Kang, Andrea Lessa Benedet, Joseph Therriault, Julie Ottoy, Pedro Rosa-Neto, Mira Chamoun, Jean-Paul Soucy, Jenna Stevenson, and Serge Gauthier

Subjects
Sexual dimorphism, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Vulnerability, Neurology (clinical), Disease, Geriatrics and Gerontology, Biology, Demography
Published
2020

35. Interaction between amyloid and neuroinflammation on apathy along the Alzheimer’s disease spectrum

Author

Melissa Savard, Cecile Tissot, Serge Gauthier, Emilie Thomas, Joseph Therriault, Sulantha Mathotaarachchi, Mira Chamoun, Pedro Rosa-Neto, Alyssa Stevenson, Tharick A. Pascoal, Firoza Z. Lussier, Min Su Kang, Nesrine Rahmouni, and Andrea Lessa Benedet

Subjects
Amyloid, Epidemiology, business.industry, Health Policy, Disease spectrum, Neuropathology, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Medicine, Apathy, Neurology (clinical), Geriatrics and Gerontology, medicine.symptom, business, Neuroscience, Neuroinflammation
Published
2020

36. Prediction of Breast Cancer Treatment-Induced Fatigue by Machine Learning Using Genome-Wide Association Data

Author

Paul Cottu, Anne-Laure Martin, Anne Boland, Cécile Charles, Jung Hun Oh, Marina Rousseau, Ines Vaz-Luis, Gwenn Menvielle, Joseph O. Deasy, Stefan Michiels, Céline Besse, Emilie Thomas, Jean-François Deleuze, Olivier Tredan, Patricia A. Ganz, Sandrine Boyault, Sibille Everhard, Fabrice Andre, Antonio Di Meglio, Ann H. Partridge, Agnès Dumas, Christelle Levy, Sangkyu Lee, Memorial Sloan Kettering Cancer Center (MSKCC), Institut Gustave Roussy (IGR), Prédicteurs moléculaires et nouvelles cibles en oncologie (PMNCO), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre Léon Bérard [Lyon], Centre National de Recherche en Génomique Humaine (CNRGH), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Fondation Synergie Lyon Cancer [Lyon], Institut Curie [Paris], Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), UNICANCER, University of California [Los Angeles] (UCLA), University of California (UC), Dana-Farber Cancer Institute [Boston], Centre d'Etude du Polymorphisme Humain (CEPH), Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Fondation Jean Dausset-Université Paris Cité (UPCité), Synergie Lyon Cancer [Lyon], and Gestionnaire, Hal Sorbonne Université

Subjects
Cancer Research, [SDV]Life Sciences [q-bio], Single-nucleotide polymorphism, Genome-wide association study, Machine learning, computer.software_genre, Article, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, medicine, Clinical endpoint, 030304 developmental biology, 0303 health sciences, Surrogate endpoint, business.industry, Cancer, medicine.disease, [SDV] Life Sciences [q-bio], Oncology, Quartile, 030220 oncology & carcinogenesis, Anxiety, Artificial intelligence, medicine.symptom, business, computer
Abstract

Background We aimed at predicting fatigue after breast cancer treatment using machine learning on clinical covariates and germline genome-wide data. Methods We accessed germline genome-wide data of 2799 early-stage breast cancer patients from the Cancer Toxicity study (NCT01993498). The primary endpoint was defined as scoring zero at diagnosis and higher than quartile 3 at 1 year after primary treatment completion on European Organization for Research and Treatment of Cancer quality-of-life questionnaires for Overall Fatigue and on the multidimensional questionnaire for Physical, Emotional, and Cognitive fatigue. First, we tested univariate associations of each endpoint with clinical variables and genome-wide variants. Then, using preselected clinical (false discovery rate < 0.05) and genomic (P Results Statistically significant clinical associations were found only with Emotional and Cognitive Fatigue, including receipt of chemotherapy, anxiety, and pain. Some single nucleotide polymorphisms had some degree of association (P Conclusions Genomic analyses in this large cohort of breast cancer survivors suggest a possible genetic role for severe Cognitive Fatigue that warrants further exploration.

Published
2019

37. Abstract P2-07-06: Multi-omics characterization of claudin-low breast tumors

Author

A-P Morel, Laurie Tonon, Alain Puisieux, Agnès Tissier, Janice Kielbassa, Roxane M. Pommier, Emilie Thomas, Alain Viari, Pierre Saintigny, and E Sohier

Subjects
Cancer Research, Oncology, Chemistry, Multi omics, Computational biology, Claudin-Low
Abstract

Breast tumors display highly heterogeneous characteristics both at transcriptional level and in term of genomic landscape. We recently reported that the differentiation status of the cell-of-origin influences the genetic route toward tumorigenesis1. Indeed, mammary stem cells exhibit the intrinsic property to tolerate the oxidative stress inherent to the oncogenic transformation through the expression of a preemptive program driven by ZEB1, an epithelial-to-mesenchymal transition (EMT)-related transcription factor, and MSRB3, a methionine sulfoxide reductase. Thereby, ZEB1-expressing tumors exhibit low level of DNA damage associated with few genomic alterations and low level of TP53 mutations. Importantly, these tumors share several transcriptional characteristics and features with normal stem cells, and with Claudin-Low (CL) molecular subtype of breast cancers. In the present work, we attempt to decipher molecular traits of CL breast tumors through multi-omics analyses of publicly available databases. This global approach allows us to highlight various CL breast tumors features as clinical attributes, gene expression, copy number alterations (CNA), somatic mutations or drug responses by differential analyses of breast tumors and cancer cell lines. Preliminary results indicate that, independently of tumor purity, CL breast tumors are mostly diploids, present a paucity of genomic rearrangements and a lower mutation rate compared to other breast tumors. They mainly, but not exclusively, show basal features and belong to the integrative cluster 4 (CNA-devoid) described by Christina Curtis and colleagues2. Concerning gene expression, CL breast tumors exhibit a frequent activation of RAS signaling pathway, an observation consistent with their sensitivity to MAPK inhibitors. Other analyses are currently ongoing and aim to better understand the biology of CL breast tumors in order to improve both the diagnosis and the therapeutic strategy used. 1. Morel A-P et al. A stemness-related ZEB1-MSRB3 axis governs cellular pliancy and breast cancer genome stability. Nature Medicine. 2017 Apr 10. 2. Curtis C et al. The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. Nature. 2012 Apr 18. Citation Format: Pommier RM, Morel A-P, Tissier A, Thomas E, Kielbassa J, Tonon L, Sohier E, Viari A, Saintigny P, Puisieux A. Multi-omics characterization of claudin-low breast tumors [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-07-06.

Published
2018

38. IC‐P‐182: AMYLOID‐DEPENDENT AND AMYLOID‐INDEPENDENT EFFECTS OF TAU ON CLINICAL STATUS

Author

Min Su Kang, Muhammad Naveed Iqbal Qureshi, Cecile Tissot, Emilie Thomas, Melissa Savard, Tharick A. Pascoal, Joseph Therriault, Andrea Lessa Benedet, Mira Chamoun, Firoza Z. Lussier, Pedro Rosa-Neto, Peter Kunach, Serge Gauthier, Sulantha Mathotaarachchi, and Gassan Massarweh

Subjects
Psychiatry and Mental health, Cellular and Molecular Neuroscience, Pathology, medicine.medical_specialty, Developmental Neuroscience, Amyloid, Epidemiology, Chemistry, Health Policy, medicine, Neurology (clinical), Geriatrics and Gerontology
Published
2019

39. Mild behavioral impairment is associated with β-amyloid but not tau or neurodegeneration in cognitively intact elderly individuals

Author

Sulantha Mathotaarachchi, Zahinoor Ismail, Serge Gauthier, I-Huang Tsai, Jean-Paul Soucy, Firoza Z. Lussier, Mira Chamoun, Cecile Tissot, Muhammad Naveed Iqbal Qureshi, Marlee Parsons, Laurie-Anne Dion, Joseph Therriault, Andrea Lessa Benedet, Pedro Rosa-Neto, Melissa Savard, Paolo Vitali, Monica Shin, Tharick A. Pascoal, Min Su Kang, Gassan Massarweh, and Emilie Thomas

Subjects
Oncology, Male, medicine.medical_specialty, Amyloid, mild behavioral impairment, Epidemiology, Standardized uptake value, tau Proteins, Disease, Positive correlation, Asymptomatic, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Developmental Neuroscience, β amyloid, Internal medicine, Elderly population, medicine, Image Processing, Computer-Assisted, Humans, tau, Aged, 030214 geriatrics, business.industry, Featured Articles, Health Policy, Neurodegeneration, neurodegeneration, Brain, Featured Article, Alzheimer's disease, medicine.disease, Magnetic Resonance Imaging, Healthy Volunteers, Psychiatry and Mental health, Positron-Emission Tomography, Positive relationship, Female, neuropsychiatric symptoms, Neurology (clinical), Geriatrics and Gerontology, medicine.symptom, business, 030217 neurology & neurosurgery, Biomarkers
Abstract

Introduction Mild behavioral impairment (MBI) is characterized by the emergence of neuropsychiatric symptoms in elderly persons. Here, we examine the associations between MBI and Alzheimer's disease (AD) biomarkers in asymptomatic elderly individuals. Methods Ninety-six cognitively normal elderly individuals underwent MRI, [18 F]AZD4694 β-amyloid-PET, and [18 F]MK6240 tau-PET. MBI was assessed using the MBI Checklist (MBI-C). Pearson's correlations and voxel-based regressions were used to evaluate the relationship between MBI-C score and [18 F]AZD4694 retention, [18 F]MK6240 retention, and gray matter (GM) volume. Results Pearson correlations revealed a positive relationship between MBI-C score and global and striatal [18 F]AZD4694 standardized uptake value ratios (SUVRs). Voxel-based regression analyses revealed a positive correlation between MBI-C score and [18 F]AZD4694 retention. No significant correlations were found between MBI-C score and [18 F]MK6240 retention or GM volume. Conclusion We demonstrate for the first time a link between MBI and early AD pathology in a cognitively intact elderly population, supporting the use of the MBI-C as a metric to enhance clinical trial enrolment.

Published
2019

40. Recollection and familiarity in schizophrenia:An ERP investigation using face recognition exclusion tasks

Author

Emilie Thomas and Fabrice Guillaume

Subjects
medicine.medical_specialty, Schizophrenia (object-oriented programming), media_common.quotation_subject, Audiology, behavioral disciplines and activities, Facial recognition system, 03 medical and health sciences, 0302 clinical medicine, Perception, medicine, Humans, Evoked Potentials, Biological Psychiatry, media_common, Facial expression, Recall, Electroencephalography, 030227 psychiatry, Psychiatry and Mental health, Expression (architecture), Face, Mental Recall, Schizophrenia, Psychology, Perceptual information, Facial Recognition, 030217 neurology & neurosurgery
Abstract

Recent studies suggest that the recollection deficit observed in schizophrenia may not be a unitary phenomenon but could depend on the information to retrieve. Here we investigated whether the nature of the perceptual information affects recollection and familiarity in schizophrenia. ERP old/new effects were explored in 20 patients with schizophrenia and 20 healthy controls during unfamiliar face exclusion tasks, with either intrinsic (expression) or extrinsic (background) information either changing or remaining the same between study and test. Schizophrenia patients rejected old faces as distractors in a greater extent than healthy controls. The FN400 old/new effect (300-500ms) was found in both groups. It was sensitive to facial expression change for healthy controls but not schizophrenia patients. In addition, the parietal old/new effect was lower for correctly excluded faces for patients, but not for controls. This points to the conclusion that schizophrenia patients discriminate between target and non-target faces on the basis of the memory strength signal corresponding to the study-test mismatch rather than the recollection of the critical information, as observed in healthy controls. This functioning can be useful when study-test perceptual mismatch must be detected but, in return, can lead to the over-exclusion of old stimuli.

Published
2019

42. Association of Apolipoprotein E ε4 With Medial Temporal Tau Independent of Amyloid-β

Author

Min Su Kang, Melissa Savard, Paramita Saha-Chaudhuri, Paolo Vitali, Serge Gauthier, Marlee Parsons, Emilie Thomas, Tharick A. Pascoal, Joseph Therriault, Pedro Rosa-Neto, Muhammad Naveed Iqbal Qureshi, Soham Rej, Cecile Tissot, Sulantha Mathotaarachchi, Mira Chamoun, Andrea Lessa Benedet, Firoza Z. Lussier, Jean-Paul Soucy, and Gassan Massarweh

Subjects
Male, Apolipoprotein E, medicine.medical_specialty, Genotype, Apolipoprotein E4, Neuroimaging, tau Proteins, Standardized uptake value, Neuropsychological Tests, 03 medical and health sciences, 0302 clinical medicine, Alzheimer Disease, Internal medicine, mental disorders, Humans, Medicine, Dementia, Cognitive Dysfunction, 030212 general & internal medicine, Young adult, Stroke, Aged, Original Investigation, Aged, 80 and over, Amyloid beta-Peptides, business.industry, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Temporal Lobe, Positron-Emission Tomography, Cohort, Female, Neurology (clinical), Alzheimer's disease, business, 030217 neurology & neurosurgery
Abstract

IMPORTANCE: Apolipoprotein E ε4 (APOEε4) is the single most important genetic risk factor for Alzheimer disease. While APOEε4 is associated with increased amyloid-β burden, its association with cerebral tau pathology has been controversial. OBJECTIVE: To determine whether APOEε4 is associated with medial temporal tau pathology independently of amyloid-β, sex, clinical status, and age. DESIGN, SETTING, AND PARTICIPANTS: This is a study of 2 cross-sectional cohorts of volunteers who were cognitively normal, had mild cognitive impairment (MCI), or had Alzheimer disease dementia: the Translational Biomarkers in Aging and Dementia (TRIAD) study (data collected between October 2017 and July 2019) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (collected between November 2015 and June 2019). The first cohort (TRIAD) comprised cognitively normal elderly participants (n = 124), participants with MCI (n = 50), and participants with Alzheimer disease (n = 50) who underwent tau positron emission tomography (PET) with fluorine 18–labeled MK6240 and amyloid-β PET with [(18)F]AZD4694. The second sample (ADNI) was composed of cognitively normal elderly participants (n = 157), participants with MCI (n = 83), and participants with Alzheimer disease (n = 25) who underwent tau PET with [(18)F]flortaucipir and amyloid-β PET with [(18)F]florbetapir. Exclusion criteria were a history of other neurological disorders, stroke, or head trauma. There were 489 eligible participants, selected based on availability of amyloid-PET, tau-PET, magnetic resonance imaging, and genotyping for APOEε4. Forty-five young adults (

Published
2020

43. P3‐338: AMYLOID AND MICROGLIAL ACTIVATION SYNERGY LEADS TO HYPOMETABOLISM IN AD BRAIN: MICROPET LONGITUDINAL STUDY

Author

Emilie Thomas, Melissa Savard, Tharick A. Pascoal, Maxime Parent, A. Claudio Cuello, Serge Gauthier, Sulantha Mathotaarachchi, Pedro Rosa-Neto, Gassan Massarweh, Min Su Kang, Antonio Aliaga, Andrea Lessa Benedet, Monica Shin, Mira Chamoun, Jean-Paul Soucy, and Joseph Therriault

Subjects
Psychiatry and Mental health, Cellular and Molecular Neuroscience, Longitudinal study, Developmental Neuroscience, Amyloid, Epidemiology, business.industry, Health Policy, Medicine, Neurology (clinical), Geriatrics and Gerontology, business, Neuroscience
Published
2018

44. P3‐096: THE SYNERGISTIC INTERACTION BETWEEN AMYLOID AND TAU DISRUPTS LOCAL AND GLOBAL RESTING STATE FMRI CONNECTIVITY

Author

Tharick A. Pascoal, Joseph Therriault, Sulantha Mathotaarachchi, Emilie Thomas, Andrea Lessa Benedet, Melissa Savard, Serge Gauthier, Min Su Kang, Pedro Rosa-Neto, and Mira Chamoun

Subjects
Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Resting state fMRI, Amyloid, Epidemiology, Chemistry, Health Policy, Neurology (clinical), Geriatrics and Gerontology, Neuroscience
Published
2018

45. P4‐107: REGIONAL PATTERNS OF TAU DEPOSITION DRIVEN BY LOCAL AMYLOID ACCUMULATION RECAPITULATE BRAAK STAGES IN AD

Author

Min Su Kang, Sulantha Mathotaarachchi, Tharick A. Pascoal, Andrea Lessa Benedet, Mira Chamoun, Melissa Savard, Joseph Therriault, Monica Shin, Emilie Thomas, Jean-Paul Soucy, Gassan Massarweh, Serge Gauthier, and Pedro Rosa-Neto

Subjects
Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Neurology (clinical), Geriatrics and Gerontology
Published
2018

46. O3‐10‐06: BRAIN EPIGENETIC CHANGES MEASURED WITH THE NOVEL [ 11 C]MARTINOSTAT PET MEDIATE THE EFFECTS OF AMYLOID AND TAU PET DEPOSITION ON COGNITION

Author

Tharick A. Pascoal, Sulantha Mathotaarachchi, Gassan Massarweh, Emilie Thomas, Mira Chamoun, Jean-Paul Soucy, Monica Shin, Melissa Savard, Serge Gauthier, Pedro Rosa-Neto, M. Mallar Chakravarty, Min Su Kang, and Joseph Therriault

Subjects
0301 basic medicine, Martinostat, Amyloid, Epidemiology, Chemistry, Health Policy, 03 medical and health sciences, Psychiatry and Mental health, Cellular and Molecular Neuroscience, 030104 developmental biology, 0302 clinical medicine, Developmental Neuroscience, Biophysics, Neurology (clinical), Epigenetics, Geriatrics and Gerontology, Deposition (chemistry), 030217 neurology & neurosurgery
Published
2018

47. IC‐P‐055: REGIONAL PATTERNS OF TAU DEPOSITION DRIVEN BY LOCAL AMYLOID ACCUMULATION RECAPITULATE BRAAK STAGES IN AD

Author

Jean-Paul Soucy, Gassan Massarweh, Pedro Rosa-Neto, Melissa Savard, Tharick A. Pascoal, Andrea Lessa Benedet, Mira Chamoun, Emilie Thomas, Min Su Kang, Monica Shin, Joseph Therriault, Serge Gauthier, and Sulantha Mathotaarachchi

Subjects
Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Amyloid, Epidemiology, Chemistry, Health Policy, Biophysics, Neurology (clinical), Geriatrics and Gerontology, Deposition (chemistry)
Published
2018

48. IC‐P‐022: LATERAL TEMPORAL AMYLOID LOAD PREDICTS PROGRESSION TO ALZHEIMER'S DEMENTIA

Author

Sulantha Mathotaarachchi, Monica Shin, Min Su Kang, Serge Gauthier, Tharick A. Pascoal, Mira Chamoun, Melissa Savard, Pedro Rosa-Neto, Emilie Thomas, Andrea Lessa Benedet, and Joseph Therriault

Subjects
Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Amyloid, Epidemiology, business.industry, Health Policy, Medicine, Alzheimer s dementia, Neurology (clinical), Geriatrics and Gerontology, business, Neuroscience
Published
2018

49. IC‐P‐054: AMYLOID AND MICROGLIAL ACTIVATION SYNERGY LEADS TO HYPOMETABOLISM IN THE AD BRAIN: MICROPET LONGITUDINAL STUDY

Author

Min Su Kang, Monica Shin, Sulantha Mathotaarachchi, Tharick A. Pascoal, Maxime J. Parent, Andrea Lessa Benedet, Joseph Therriault, Mira Chamoun, Melissa Savard, Emilie Thomas, Antonio Aliaga, Gassan Massarweh, Jean-Paul Soucy, Serge Gauthier, A. Claudio Cuello, and Pedro Rosa-Neto

Subjects
Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Neurology (clinical), Geriatrics and Gerontology
Published
2018

50. P3‐441: LOGICAL MEMORY DEFICITS ACROSS ALZHEIMER'S DISEASE SPECTRUM ARE ASSOCIATED WITH PATTERNS OF A TAU PROPAGATION PREDICTED BY BRAAK STAGING

Author

Sulantha Mathotaarachchi, Tharick A. Pascoal, Andrea Lessa Benedet, Min Su Kang, Mira Chamoun, Joseph Therriault, Melissa Savard, Emilie Thomas, Monica Shin, Vladimir S. Fonov, Jean-Paul Soucy, Serge Gauthier, and Pedro Rosa-Neto

Subjects
Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Neurology (clinical), Geriatrics and Gerontology
Published
2018

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