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21 results on '"Farshidfar, Farshad"'

1. Germline genetic contribution to the immune landscape of cancer

Author

Barcelona Supercomputing Center, Sayaman, Rosalyn W., Saad, Mohamad, Thorsson, Vésteinn, Hu, Donglei, Hendrickx, Wouter, Roelands, Jessica, Porta Pardo, Eduard, Mokrab, Younes, Farshidfar, Farshad, Kirchhoff, Tomas, Sweis, Randy F., Bathe, Oliver F., Heimann, Carolina, Campbell, Michael J., Stretch, Cynthia, Huntsman, Scott, Graff, Rebecca E., Syed, Najeeb, Radvanyi, Laszlo, Shelley, Simon, Wolf, Denise, Marincola, Francesco M., Ceccarelli, Michele, Galon, Jérôme, Ziv, Elad, Bedognetti, Davide, Barcelona Supercomputing Center, Sayaman, Rosalyn W., Saad, Mohamad, Thorsson, Vésteinn, Hu, Donglei, Hendrickx, Wouter, Roelands, Jessica, Porta Pardo, Eduard, Mokrab, Younes, Farshidfar, Farshad, Kirchhoff, Tomas, Sweis, Randy F., Bathe, Oliver F., Heimann, Carolina, Campbell, Michael J., Stretch, Cynthia, Huntsman, Scott, Graff, Rebecca E., Syed, Najeeb, Radvanyi, Laszlo, Shelley, Simon, Wolf, Denise, Marincola, Francesco M., Ceccarelli, Michele, Galon, Jérôme, Ziv, Elad, and Bedognetti, Davide

Abstract

Understanding the contribution of the host’s genetic background to cancer immunity may lead to improved stratification for immunotherapy and to the identification of novel therapeutic targets. We investigated the effect of common and rare germline variants on 139 well-defined immune traits in ∼9000 cancer patients enrolled in TCGA. High heritability was observed for estimates of NK cell and T cell subset infiltration and for interferon signaling. Common variants of IFIH1, TMEM173 (STING1), and TMEM108 were associated with differential interferon signaling and variants mapping to RBL1 correlated with T cell subset abundance. Pathogenic or likely pathogenic variants in BRCA1 and in genes involved in telomere stabilization and Wnt-β-catenin also acted as immune modulators. Our findings provide evidence for the impact of germline genetics on the composition and functional orientation of the tumor immune microenvironment. The curated datasets, variants, and genes identified provide a resource toward further understanding of tumor-immune interactions., We are grateful to the Society for Immunotherapy of Cancer (SITC) for the logistical support of the investigator meeting within the SITC Cancer Immune Responsiveness Workshop (San Francisco CA, US, April 2018; Houston, TX, US, May 2019). We are also grateful to Noah Zaitlen and Andy Dahl for useful discussions on heritability interaction analyses. This work was funded in part by the National Institutes of Health R01CA227466 and K24CA169004 to EZ and T32CA221709 postdoctoral fellowship to RWS, Qatar National Research Fund (QNRF) NPRP11S-0121-180351 grant and the Sidra Precision Medicine Program internal grant (SDR100035 and SDR400023) to DB, Associazione Italiana per la Ricerca sul cancro (AIRC) grant IG2018-21846 to MC, the Cancer Research Institute funding to VT, and the Fundació Bancaria La Caixa, a La Caixa Junior Leader Fellowship (LCF/BQ/PI18/11630003) to EP-P., Peer Reviewed, Postprint (author's final draft)

Published
2021

2. Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH-Mutant Molecular Profiles.

Author

Farshidfar, Farshad, Farshidfar, Farshad, Zheng, Siyuan, Gingras, Marie-Claude, Newton, Yulia, Shih, Juliann, Robertson, A Gordon, Hinoue, Toshinori, Hoadley, Katherine A, Gibb, Ewan A, Roszik, Jason, Covington, Kyle R, Wu, Chia-Chin, Shinbrot, Eve, Stransky, Nicolas, Hegde, Apurva, Yang, Ju Dong, Reznik, Ed, Sadeghi, Sara, Pedamallu, Chandra Sekhar, Ojesina, Akinyemi I, Hess, Julian M, Auman, J Todd, Rhie, Suhn K, Bowlby, Reanne, Borad, Mitesh J, Cancer Genome Atlas Network, Zhu, Andrew X, Stuart, Josh M, Sander, Chris, Akbani, Rehan, Cherniack, Andrew D, Deshpande, Vikram, Mounajjed, Taofic, Foo, Wai Chin, Torbenson, Michael S, Kleiner, David E, Laird, Peter W, Wheeler, David A, McRee, Autumn J, Bathe, Oliver F, Andersen, Jesper B, Bardeesy, Nabeel, Roberts, Lewis R, Kwong, Lawrence N, Farshidfar, Farshad, Farshidfar, Farshad, Zheng, Siyuan, Gingras, Marie-Claude, Newton, Yulia, Shih, Juliann, Robertson, A Gordon, Hinoue, Toshinori, Hoadley, Katherine A, Gibb, Ewan A, Roszik, Jason, Covington, Kyle R, Wu, Chia-Chin, Shinbrot, Eve, Stransky, Nicolas, Hegde, Apurva, Yang, Ju Dong, Reznik, Ed, Sadeghi, Sara, Pedamallu, Chandra Sekhar, Ojesina, Akinyemi I, Hess, Julian M, Auman, J Todd, Rhie, Suhn K, Bowlby, Reanne, Borad, Mitesh J, Cancer Genome Atlas Network, Zhu, Andrew X, Stuart, Josh M, Sander, Chris, Akbani, Rehan, Cherniack, Andrew D, Deshpande, Vikram, Mounajjed, Taofic, Foo, Wai Chin, Torbenson, Michael S, Kleiner, David E, Laird, Peter W, Wheeler, David A, McRee, Autumn J, Bathe, Oliver F, Andersen, Jesper B, Bardeesy, Nabeel, Roberts, Lewis R, and Kwong, Lawrence N

Abstract

Cholangiocarcinoma (CCA) is an aggressive malignancy of the bile ducts, with poor prognosis and limited treatment options. Here, we describe the integrated analysis of somatic mutations, RNA expression, copy number, and DNA methylation by The Cancer Genome Atlas of a set of predominantly intrahepatic CCA cases and propose a molecular classification scheme. We identified an IDH mutant-enriched subtype with distinct molecular features including low expression of chromatin modifiers, elevated expression of mitochondrial genes, and increased mitochondrial DNA copy number. Leveraging the multi-platform data, we observed that ARID1A exhibited DNA hypermethylation and decreased expression in the IDH mutant subtype. More broadly, we found that IDH mutations are associated with an expanded histological spectrum of liver tumors with molecular features that stratify with CCA. Our studies reveal insights into the molecular pathogenesis and heterogeneity of cholangiocarcinoma and provide classification information of potential therapeutic significance.

Published
2017

3. Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH-Mutant Molecular Profiles.

Author

Farshidfar, Farshad, Farshidfar, Farshad, Zheng, Siyuan, Gingras, Marie-Claude, Newton, Yulia, Shih, Juliann, Robertson, A Gordon, Hinoue, Toshinori, Hoadley, Katherine A, Gibb, Ewan A, Roszik, Jason, Covington, Kyle R, Wu, Chia-Chin, Shinbrot, Eve, Stransky, Nicolas, Hegde, Apurva, Yang, Ju Dong, Reznik, Ed, Sadeghi, Sara, Pedamallu, Chandra Sekhar, Ojesina, Akinyemi I, Hess, Julian M, Auman, J Todd, Rhie, Suhn K, Bowlby, Reanne, Borad, Mitesh J, Cancer Genome Atlas Network, Zhu, Andrew X, Stuart, Josh M, Sander, Chris, Akbani, Rehan, Cherniack, Andrew D, Deshpande, Vikram, Mounajjed, Taofic, Foo, Wai Chin, Torbenson, Michael S, Kleiner, David E, Laird, Peter W, Wheeler, David A, McRee, Autumn J, Bathe, Oliver F, Andersen, Jesper B, Bardeesy, Nabeel, Roberts, Lewis R, Kwong, Lawrence N, Farshidfar, Farshad, Farshidfar, Farshad, Zheng, Siyuan, Gingras, Marie-Claude, Newton, Yulia, Shih, Juliann, Robertson, A Gordon, Hinoue, Toshinori, Hoadley, Katherine A, Gibb, Ewan A, Roszik, Jason, Covington, Kyle R, Wu, Chia-Chin, Shinbrot, Eve, Stransky, Nicolas, Hegde, Apurva, Yang, Ju Dong, Reznik, Ed, Sadeghi, Sara, Pedamallu, Chandra Sekhar, Ojesina, Akinyemi I, Hess, Julian M, Auman, J Todd, Rhie, Suhn K, Bowlby, Reanne, Borad, Mitesh J, Cancer Genome Atlas Network, Zhu, Andrew X, Stuart, Josh M, Sander, Chris, Akbani, Rehan, Cherniack, Andrew D, Deshpande, Vikram, Mounajjed, Taofic, Foo, Wai Chin, Torbenson, Michael S, Kleiner, David E, Laird, Peter W, Wheeler, David A, McRee, Autumn J, Bathe, Oliver F, Andersen, Jesper B, Bardeesy, Nabeel, Roberts, Lewis R, and Kwong, Lawrence N

Abstract

Cholangiocarcinoma (CCA) is an aggressive malignancy of the bile ducts, with poor prognosis and limited treatment options. Here, we describe the integrated analysis of somatic mutations, RNA expression, copy number, and DNA methylation by The Cancer Genome Atlas of a set of predominantly intrahepatic CCA cases and propose a molecular classification scheme. We identified an IDH mutant-enriched subtype with distinct molecular features including low expression of chromatin modifiers, elevated expression of mitochondrial genes, and increased mitochondrial DNA copy number. Leveraging the multi-platform data, we observed that ARID1A exhibited DNA hypermethylation and decreased expression in the IDH mutant subtype. More broadly, we found that IDH mutations are associated with an expanded histological spectrum of liver tumors with molecular features that stratify with CCA. Our studies reveal insights into the molecular pathogenesis and heterogeneity of cholangiocarcinoma and provide classification information of potential therapeutic significance.

Published
2017

4. The Immune Landscape of Cancer

Author

Thorsson, Vésteinn, Thorsson, Vésteinn, Gibbs, David L, Brown, Scott D, Wolf, Denise, Bortone, Dante S, Yang, Tai-Hsien Ou, Porta-Pardo, Eduard, Gao, Galen F, Plaisier, Christopher L, Eddy, James A, Ziv, Elad, Culhane, Aedin C, Paull, Evan O, Sivakumar, IK Ashok, Gentles, Andrew J, Malhotra, Raunaq, Farshidfar, Farshad, Colaprico, Antonio, Parker, Joel S, Mose, Lisle E, Vo, Nam Sy, Liu, Jianfang, Liu, Yuexin, Rader, Janet, Dhankani, Varsha, Reynolds, Sheila M, Bowlby, Reanne, Califano, Andrea, Cherniack, Andrew D, Anastassiou, Dimitris, Bedognetti, Davide, Mokrab, Younes, Newman, Aaron M, Rao, Arvind, Chen, Ken, Krasnitz, Alexander, Hu, Hai, Malta, Tathiane M, Noushmehr, Houtan, Pedamallu, Chandra Sekhar, Bullman, Susan, Ojesina, Akinyemi I, Lamb, Andrew, Zhou, Wanding, Shen, Hui, Choueiri, Toni K, Weinstein, John N, Guinney, Justin, Saltz, Joel, Holt, Robert A, Rabkin, Charles S, Network, The Cancer Genome Atlas Research, Caesar-Johnson, Samantha J, Demchok, John A, Felau, Ina, Kasapi, Melpomeni, Ferguson, Martin L, Hutter, Carolyn M, Sofia, Heidi J, Tarnuzzer, Roy, Wang, Zhining, Yang, Liming, Zenklusen, Jean C, Zhang, Jiashan, Chudamani, Sudha, Liu, Jia, Lolla, Laxmi, Naresh, Rashi, Pihl, Todd, Sun, Qiang, Wan, Yunhu, Wu, Ye, Cho, Juok, DeFreitas, Timothy, Frazer, Scott, Gehlenborg, Nils, Getz, Gad, Heiman, David I, Kim, Jaegil, Lawrence, Michael S, Lin, Pei, Meier, Sam, Noble, Michael S, Saksena, Gordon, Voet, Doug, Zhang, Hailei, Bernard, Brady, Chambwe, Nyasha, Knijnenburg, Theo, Kramer, Roger, Leinonen, Kalle, Miller, Michael, Reynolds, Sheila, Shmulevich, Ilya, Thorsson, Vesteinn, Zhang, Wei, Akbani, Rehan, Broom, Bradley M, Thorsson, Vésteinn, Thorsson, Vésteinn, Gibbs, David L, Brown, Scott D, Wolf, Denise, Bortone, Dante S, Yang, Tai-Hsien Ou, Porta-Pardo, Eduard, Gao, Galen F, Plaisier, Christopher L, Eddy, James A, Ziv, Elad, Culhane, Aedin C, Paull, Evan O, Sivakumar, IK Ashok, Gentles, Andrew J, Malhotra, Raunaq, Farshidfar, Farshad, Colaprico, Antonio, Parker, Joel S, Mose, Lisle E, Vo, Nam Sy, Liu, Jianfang, Liu, Yuexin, Rader, Janet, Dhankani, Varsha, Reynolds, Sheila M, Bowlby, Reanne, Califano, Andrea, Cherniack, Andrew D, Anastassiou, Dimitris, Bedognetti, Davide, Mokrab, Younes, Newman, Aaron M, Rao, Arvind, Chen, Ken, Krasnitz, Alexander, Hu, Hai, Malta, Tathiane M, Noushmehr, Houtan, Pedamallu, Chandra Sekhar, Bullman, Susan, Ojesina, Akinyemi I, Lamb, Andrew, Zhou, Wanding, Shen, Hui, Choueiri, Toni K, Weinstein, John N, Guinney, Justin, Saltz, Joel, Holt, Robert A, Rabkin, Charles S, Network, The Cancer Genome Atlas Research, Caesar-Johnson, Samantha J, Demchok, John A, Felau, Ina, Kasapi, Melpomeni, Ferguson, Martin L, Hutter, Carolyn M, Sofia, Heidi J, Tarnuzzer, Roy, Wang, Zhining, Yang, Liming, Zenklusen, Jean C, Zhang, Jiashan, Chudamani, Sudha, Liu, Jia, Lolla, Laxmi, Naresh, Rashi, Pihl, Todd, Sun, Qiang, Wan, Yunhu, Wu, Ye, Cho, Juok, DeFreitas, Timothy, Frazer, Scott, Gehlenborg, Nils, Getz, Gad, Heiman, David I, Kim, Jaegil, Lawrence, Michael S, Lin, Pei, Meier, Sam, Noble, Michael S, Saksena, Gordon, Voet, Doug, Zhang, Hailei, Bernard, Brady, Chambwe, Nyasha, Knijnenburg, Theo, Kramer, Roger, Leinonen, Kalle, Miller, Michael, Reynolds, Sheila, Shmulevich, Ilya, Thorsson, Vesteinn, Zhang, Wei, Akbani, Rehan, and Broom, Bradley M

Abstract

(Immunity 48, 812–830.e1–e14; April 17, 2018) In the originally published version of this article, the authors neglected to include Younes Mokrab and Aaron M. Newman as co-authors and misspelled the names of authors Charles S. Rabkin and Ilya Shmulevich. The author names have been corrected here and online. In addition, the concluding sentence of the subsection “Immune Signature Compilation” in the Method Details in the original published article was deemed unclear because it did not specify differences among the gene set scoring methods. The concluding sentences now reads “Gene sets from Bindea et al., Senbabaoglu et al., and the MSigDB C7 collection were scored using single-sample gene set enrichment (ssGSEA) analysis (Barbie et al., 2009), as implemented in the GSVA R package (Hänzelmann et al., 2013). All other signatures were scored using methods found in the associated citations.”

Published
2019

5. Molecular Characterization and Clinical Relevance of Metabolic Expression Subtypes in Human Cancers.

Author

Peng, Xinxin, Peng, Xinxin, Chen, Zhongyuan, Farshidfar, Farshad, Xu, Xiaoyan, Lorenzi, Philip L, Wang, Yumeng, Cheng, Feixiong, Tan, Lin, Mojumdar, Kamalika, Du, Di, Ge, Zhongqi, Li, Jun, Thomas, George V, Birsoy, Kivanc, Liu, Lingxiang, Zhang, Huiwen, Zhao, Zhongming, Marchand, Calena, Weinstein, John N, Cancer Genome Atlas Research Network, Bathe, Oliver F, Liang, Han, Peng, Xinxin, Peng, Xinxin, Chen, Zhongyuan, Farshidfar, Farshad, Xu, Xiaoyan, Lorenzi, Philip L, Wang, Yumeng, Cheng, Feixiong, Tan, Lin, Mojumdar, Kamalika, Du, Di, Ge, Zhongqi, Li, Jun, Thomas, George V, Birsoy, Kivanc, Liu, Lingxiang, Zhang, Huiwen, Zhao, Zhongming, Marchand, Calena, Weinstein, John N, Cancer Genome Atlas Research Network, Bathe, Oliver F, and Liang, Han

Abstract

Metabolic reprogramming provides critical information for clinical oncology. Using molecular data of 9,125 patient samples from The Cancer Genome Atlas, we identified tumor subtypes in 33 cancer types based on mRNA expression patterns of seven major metabolic processes and assessed their clinical relevance. Our metabolic expression subtypes correlated extensively with clinical outcome: subtypes with upregulated carbohydrate, nucleotide, and vitamin/cofactor metabolism most consistently correlated with worse prognosis, whereas subtypes with upregulated lipid metabolism showed the opposite. Metabolic subtypes correlated with diverse somatic drivers but exhibited effects convergent on cancer hallmark pathways and were modulated by highly recurrent master regulators across cancer types. As a proof-of-concept example, we demonstrated that knockdown of SNAI1 or RUNX1-master regulators of carbohydrate metabolic subtypes-modulates metabolic activity and drug sensitivity. Our study provides a system-level view of metabolic heterogeneity within and across cancer types and identifies pathway cross-talk, suggesting related prognostic, therapeutic, and predictive utility.

Published
2018

6. The Immune Landscape of Cancer

Author

Thorsson, Vésteinn, Gibbs, David L., Brown, Scott D., Wolf, Denise, Bortone, Dante S., Ou Yang, Tai Hsien, Porta-Pardo, Eduard, Gao, Galen F., Plaisier, Christopher L., Eddy, James A., Ziv, Elad, Culhane, Aedin C., Paull, Evan O., Sivakumar, I. K.Ashok, Gentles, Andrew J., Malhotra, Raunaq, Farshidfar, Farshad, Colaprico, Antonio, Parker, Joel S., Mose, Lisle E., Vo, Nam Sy, Liu, Jianfang, Liu, Yuexin, Rader, Janet, Dhankani, Varsha, Reynolds, Sheila M., Bowlby, Reanne, Califano, Andrea, Cherniack, Andrew D., Anastassiou, Dimitris, Bedognetti, Davide, Rao, Arvind, Chen, Ken, Krasnitz, Alexander, Hu, Hai, Malta, Tathiane M., Noushmehr, Houtan, Pedamallu, Chandra Sekhar, Bullman, Susan, Ojesina, Akinyemi I., Lamb, Andrew, Zhou, Wanding, Shen, Hui, Choueiri, Toni K., Weinstein, John N., Guinney, Justin, Saltz, Joel, Holt, Robert, Zhang, Jiashan (Julia), de Krijger, Ronald, The Cancer Genome Atlas Research Network, Thorsson, Vésteinn, Gibbs, David L., Brown, Scott D., Wolf, Denise, Bortone, Dante S., Ou Yang, Tai Hsien, Porta-Pardo, Eduard, Gao, Galen F., Plaisier, Christopher L., Eddy, James A., Ziv, Elad, Culhane, Aedin C., Paull, Evan O., Sivakumar, I. K.Ashok, Gentles, Andrew J., Malhotra, Raunaq, Farshidfar, Farshad, Colaprico, Antonio, Parker, Joel S., Mose, Lisle E., Vo, Nam Sy, Liu, Jianfang, Liu, Yuexin, Rader, Janet, Dhankani, Varsha, Reynolds, Sheila M., Bowlby, Reanne, Califano, Andrea, Cherniack, Andrew D., Anastassiou, Dimitris, Bedognetti, Davide, Rao, Arvind, Chen, Ken, Krasnitz, Alexander, Hu, Hai, Malta, Tathiane M., Noushmehr, Houtan, Pedamallu, Chandra Sekhar, Bullman, Susan, Ojesina, Akinyemi I., Lamb, Andrew, Zhou, Wanding, Shen, Hui, Choueiri, Toni K., Weinstein, John N., Guinney, Justin, Saltz, Joel, Holt, Robert, Zhang, Jiashan (Julia), de Krijger, Ronald, and The Cancer Genome Atlas Research Network

Published
2018

7. Comparative Molecular Analysis of Gastrointestinal Adenocarcinomas

Author

Liu, Yang, Sethi, Nilay S, Hinoue, Toshinori, Schneider, Barbara G, Cherniack, Andrew D, Sanchez-Vega, Francisco, Seoane, Jose A, Farshidfar, Farshad, Bowlby, Reanne, Islam, Mirazul, Kim, Jaegil, Chatila, Walid, Akbani, Rehan, Kanchi, Rupa S, Rabkin, Charles S, Willis, Joseph E, Wang, Kenneth K, McCall, Shannon J, Mishra, Lopa, Ojesina, Akinyemi I, Bullman, Susan, Pedamallu, Chandra Sekhar, Lazar, Alexander J, Sakai, Ryo, Thorsson, Vésteinn, Bass, Adam J, Laird, Peter W, Cancer Genome Atlas Research Network, Liu, Yang, Sethi, Nilay S, Hinoue, Toshinori, Schneider, Barbara G, Cherniack, Andrew D, Sanchez-Vega, Francisco, Seoane, Jose A, Farshidfar, Farshad, Bowlby, Reanne, Islam, Mirazul, Kim, Jaegil, Chatila, Walid, Akbani, Rehan, Kanchi, Rupa S, Rabkin, Charles S, Willis, Joseph E, Wang, Kenneth K, McCall, Shannon J, Mishra, Lopa, Ojesina, Akinyemi I, Bullman, Susan, Pedamallu, Chandra Sekhar, Lazar, Alexander J, Sakai, Ryo, Thorsson, Vésteinn, Bass, Adam J, Laird, Peter W, and Cancer Genome Atlas Research Network

Published
2018

8. The Immune Landscape of Cancer

Author

Thorsson, Vésteinn, Gibbs, David L., Brown, Scott D., Wolf, Denise, Bortone, Dante S., Ou Yang, Tai Hsien, Porta-Pardo, Eduard, Gao, Galen F., Plaisier, Christopher L., Eddy, James A., Ziv, Elad, Culhane, Aedin C., Paull, Evan O., Sivakumar, I. K.Ashok, Gentles, Andrew J., Malhotra, Raunaq, Farshidfar, Farshad, Colaprico, Antonio, Parker, Joel S., Mose, Lisle E., Vo, Nam Sy, Liu, Jianfang, Liu, Yuexin, Rader, Janet, Dhankani, Varsha, Reynolds, Sheila M., Bowlby, Reanne, Califano, Andrea, Cherniack, Andrew D., Anastassiou, Dimitris, Bedognetti, Davide, Rao, Arvind, Chen, Ken, Krasnitz, Alexander, Hu, Hai, Malta, Tathiane M., Noushmehr, Houtan, Pedamallu, Chandra Sekhar, Bullman, Susan, Ojesina, Akinyemi I., Lamb, Andrew, Zhou, Wanding, Shen, Hui, Choueiri, Toni K., Weinstein, John N., Guinney, Justin, Saltz, Joel, Holt, Robert, Zhang, Jiashan (Julia), de Krijger, Ronald, The Cancer Genome Atlas Research Network, Thorsson, Vésteinn, Gibbs, David L., Brown, Scott D., Wolf, Denise, Bortone, Dante S., Ou Yang, Tai Hsien, Porta-Pardo, Eduard, Gao, Galen F., Plaisier, Christopher L., Eddy, James A., Ziv, Elad, Culhane, Aedin C., Paull, Evan O., Sivakumar, I. K.Ashok, Gentles, Andrew J., Malhotra, Raunaq, Farshidfar, Farshad, Colaprico, Antonio, Parker, Joel S., Mose, Lisle E., Vo, Nam Sy, Liu, Jianfang, Liu, Yuexin, Rader, Janet, Dhankani, Varsha, Reynolds, Sheila M., Bowlby, Reanne, Califano, Andrea, Cherniack, Andrew D., Anastassiou, Dimitris, Bedognetti, Davide, Rao, Arvind, Chen, Ken, Krasnitz, Alexander, Hu, Hai, Malta, Tathiane M., Noushmehr, Houtan, Pedamallu, Chandra Sekhar, Bullman, Susan, Ojesina, Akinyemi I., Lamb, Andrew, Zhou, Wanding, Shen, Hui, Choueiri, Toni K., Weinstein, John N., Guinney, Justin, Saltz, Joel, Holt, Robert, Zhang, Jiashan (Julia), de Krijger, Ronald, and The Cancer Genome Atlas Research Network

Published
2018

9. Comparative Molecular Analysis of Gastrointestinal Adenocarcinomas

Author

Liu, Yang, Sethi, Nilay S, Hinoue, Toshinori, Schneider, Barbara G, Cherniack, Andrew D, Sanchez-Vega, Francisco, Seoane, Jose A, Farshidfar, Farshad, Bowlby, Reanne, Islam, Mirazul, Kim, Jaegil, Chatila, Walid, Akbani, Rehan, Kanchi, Rupa S, Rabkin, Charles S, Willis, Joseph E, Wang, Kenneth K, McCall, Shannon J, Mishra, Lopa, Ojesina, Akinyemi I, Bullman, Susan, Pedamallu, Chandra Sekhar, Lazar, Alexander J, Sakai, Ryo, Thorsson, Vésteinn, Bass, Adam J, Laird, Peter W, Cancer Genome Atlas Research Network, Liu, Yang, Sethi, Nilay S, Hinoue, Toshinori, Schneider, Barbara G, Cherniack, Andrew D, Sanchez-Vega, Francisco, Seoane, Jose A, Farshidfar, Farshad, Bowlby, Reanne, Islam, Mirazul, Kim, Jaegil, Chatila, Walid, Akbani, Rehan, Kanchi, Rupa S, Rabkin, Charles S, Willis, Joseph E, Wang, Kenneth K, McCall, Shannon J, Mishra, Lopa, Ojesina, Akinyemi I, Bullman, Susan, Pedamallu, Chandra Sekhar, Lazar, Alexander J, Sakai, Ryo, Thorsson, Vésteinn, Bass, Adam J, Laird, Peter W, and Cancer Genome Atlas Research Network

Published
2018

10. Molecular Characterization and Clinical Relevance of Metabolic Expression Subtypes in Human Cancers.

Author

Peng, Xinxin, Peng, Xinxin, Chen, Zhongyuan, Farshidfar, Farshad, Xu, Xiaoyan, Lorenzi, Philip L, Wang, Yumeng, Cheng, Feixiong, Tan, Lin, Mojumdar, Kamalika, Du, Di, Ge, Zhongqi, Li, Jun, Thomas, George V, Birsoy, Kivanc, Liu, Lingxiang, Zhang, Huiwen, Zhao, Zhongming, Marchand, Calena, Weinstein, John N, Cancer Genome Atlas Research Network, Bathe, Oliver F, Liang, Han, Peng, Xinxin, Peng, Xinxin, Chen, Zhongyuan, Farshidfar, Farshad, Xu, Xiaoyan, Lorenzi, Philip L, Wang, Yumeng, Cheng, Feixiong, Tan, Lin, Mojumdar, Kamalika, Du, Di, Ge, Zhongqi, Li, Jun, Thomas, George V, Birsoy, Kivanc, Liu, Lingxiang, Zhang, Huiwen, Zhao, Zhongming, Marchand, Calena, Weinstein, John N, Cancer Genome Atlas Research Network, Bathe, Oliver F, and Liang, Han

Abstract

Metabolic reprogramming provides critical information for clinical oncology. Using molecular data of 9,125 patient samples from The Cancer Genome Atlas, we identified tumor subtypes in 33 cancer types based on mRNA expression patterns of seven major metabolic processes and assessed their clinical relevance. Our metabolic expression subtypes correlated extensively with clinical outcome: subtypes with upregulated carbohydrate, nucleotide, and vitamin/cofactor metabolism most consistently correlated with worse prognosis, whereas subtypes with upregulated lipid metabolism showed the opposite. Metabolic subtypes correlated with diverse somatic drivers but exhibited effects convergent on cancer hallmark pathways and were modulated by highly recurrent master regulators across cancer types. As a proof-of-concept example, we demonstrated that knockdown of SNAI1 or RUNX1-master regulators of carbohydrate metabolic subtypes-modulates metabolic activity and drug sensitivity. Our study provides a system-level view of metabolic heterogeneity within and across cancer types and identifies pathway cross-talk, suggesting related prognostic, therapeutic, and predictive utility.

Published
2018

11. The Immune Landscape of Cancer

Author

Thorsson, Vésteinn, Gibbs, David L., Brown, Scott D., Wolf, Denise, Bortone, Dante S., Ou Yang, Tai Hsien, Porta-Pardo, Eduard, Gao, Galen F., Plaisier, Christopher L., Eddy, James A., Ziv, Elad, Culhane, Aedin C., Paull, Evan O., Sivakumar, I. K.Ashok, Gentles, Andrew J., Malhotra, Raunaq, Farshidfar, Farshad, Colaprico, Antonio, Parker, Joel S., Mose, Lisle E., Vo, Nam Sy, Liu, Jianfang, Liu, Yuexin, Rader, Janet, Dhankani, Varsha, Reynolds, Sheila M., Bowlby, Reanne, Califano, Andrea, Cherniack, Andrew D., Anastassiou, Dimitris, Bedognetti, Davide, Rao, Arvind, Chen, Ken, Krasnitz, Alexander, Hu, Hai, Malta, Tathiane M., Noushmehr, Houtan, Pedamallu, Chandra Sekhar, Bullman, Susan, Ojesina, Akinyemi I., Lamb, Andrew, Zhou, Wanding, Shen, Hui, Choueiri, Toni K., Weinstein, John N., Guinney, Justin, Saltz, Joel, Holt, Robert, Zhang, Jiashan (Julia), de Krijger, Ronald, The Cancer Genome Atlas Research Network, Thorsson, Vésteinn, Gibbs, David L., Brown, Scott D., Wolf, Denise, Bortone, Dante S., Ou Yang, Tai Hsien, Porta-Pardo, Eduard, Gao, Galen F., Plaisier, Christopher L., Eddy, James A., Ziv, Elad, Culhane, Aedin C., Paull, Evan O., Sivakumar, I. K.Ashok, Gentles, Andrew J., Malhotra, Raunaq, Farshidfar, Farshad, Colaprico, Antonio, Parker, Joel S., Mose, Lisle E., Vo, Nam Sy, Liu, Jianfang, Liu, Yuexin, Rader, Janet, Dhankani, Varsha, Reynolds, Sheila M., Bowlby, Reanne, Califano, Andrea, Cherniack, Andrew D., Anastassiou, Dimitris, Bedognetti, Davide, Rao, Arvind, Chen, Ken, Krasnitz, Alexander, Hu, Hai, Malta, Tathiane M., Noushmehr, Houtan, Pedamallu, Chandra Sekhar, Bullman, Susan, Ojesina, Akinyemi I., Lamb, Andrew, Zhou, Wanding, Shen, Hui, Choueiri, Toni K., Weinstein, John N., Guinney, Justin, Saltz, Joel, Holt, Robert, Zhang, Jiashan (Julia), de Krijger, Ronald, and The Cancer Genome Atlas Research Network

Published
2018

12. Comparative Molecular Analysis of Gastrointestinal Adenocarcinomas

Author

Liu, Yang, Sethi, Nilay S, Hinoue, Toshinori, Schneider, Barbara G, Cherniack, Andrew D, Sanchez-Vega, Francisco, Seoane, Jose A, Farshidfar, Farshad, Bowlby, Reanne, Islam, Mirazul, Kim, Jaegil, Chatila, Walid, Akbani, Rehan, Kanchi, Rupa S, Rabkin, Charles S, Willis, Joseph E, Wang, Kenneth K, McCall, Shannon J, Mishra, Lopa, Ojesina, Akinyemi I, Bullman, Susan, Pedamallu, Chandra Sekhar, Lazar, Alexander J, Sakai, Ryo, Thorsson, Vésteinn, Bass, Adam J, Laird, Peter W, Cancer Genome Atlas Research Network, Liu, Yang, Sethi, Nilay S, Hinoue, Toshinori, Schneider, Barbara G, Cherniack, Andrew D, Sanchez-Vega, Francisco, Seoane, Jose A, Farshidfar, Farshad, Bowlby, Reanne, Islam, Mirazul, Kim, Jaegil, Chatila, Walid, Akbani, Rehan, Kanchi, Rupa S, Rabkin, Charles S, Willis, Joseph E, Wang, Kenneth K, McCall, Shannon J, Mishra, Lopa, Ojesina, Akinyemi I, Bullman, Susan, Pedamallu, Chandra Sekhar, Lazar, Alexander J, Sakai, Ryo, Thorsson, Vésteinn, Bass, Adam J, Laird, Peter W, and Cancer Genome Atlas Research Network

Published
2018

13. Comparative Molecular Analysis of Gastrointestinal Adenocarcinomas.

Author

Liu, Yang, Liu, Yang, Sethi, Nilay S, Hinoue, Toshinori, Schneider, Barbara G, Cherniack, Andrew D, Sanchez-Vega, Francisco, Seoane, Jose A, Farshidfar, Farshad, Bowlby, Reanne, Islam, Mirazul, Kim, Jaegil, Chatila, Walid, Akbani, Rehan, Kanchi, Rupa S, Rabkin, Charles S, Willis, Joseph E, Wang, Kenneth K, McCall, Shannon J, Mishra, Lopa, Ojesina, Akinyemi I, Bullman, Susan, Pedamallu, Chandra Sekhar, Lazar, Alexander J, Sakai, Ryo, Cancer Genome Atlas Research Network, Thorsson, Vésteinn, Bass, Adam J, Laird, Peter W, Liu, Yang, Liu, Yang, Sethi, Nilay S, Hinoue, Toshinori, Schneider, Barbara G, Cherniack, Andrew D, Sanchez-Vega, Francisco, Seoane, Jose A, Farshidfar, Farshad, Bowlby, Reanne, Islam, Mirazul, Kim, Jaegil, Chatila, Walid, Akbani, Rehan, Kanchi, Rupa S, Rabkin, Charles S, Willis, Joseph E, Wang, Kenneth K, McCall, Shannon J, Mishra, Lopa, Ojesina, Akinyemi I, Bullman, Susan, Pedamallu, Chandra Sekhar, Lazar, Alexander J, Sakai, Ryo, Cancer Genome Atlas Research Network, Thorsson, Vésteinn, Bass, Adam J, and Laird, Peter W

Abstract

We analyzed 921 adenocarcinomas of the esophagus, stomach, colon, and rectum to examine shared and distinguishing molecular characteristics of gastrointestinal tract adenocarcinomas (GIACs). Hypermutated tumors were distinct regardless of cancer type and comprised those enriched for insertions/deletions, representing microsatellite instability cases with epigenetic silencing of MLH1 in the context of CpG island methylator phenotype, plus tumors with elevated single-nucleotide variants associated with mutations in POLE. Tumors with chromosomal instability were diverse, with gastroesophageal adenocarcinomas harboring fragmented genomes associated with genomic doubling and distinct mutational signatures. We identified a group of tumors in the colon and rectum lacking hypermutation and aneuploidy termed genome stable and enriched in DNA hypermethylation and mutations in KRAS, SOX9, and PCBP1.

Published
2018

14. The Immune Landscape of Cancer

Author

Onderzoeksgroep 6, Pathologie Pathologen staf, Thorsson, Vésteinn, Gibbs, David L., Brown, Scott D., Wolf, Denise, Bortone, Dante S., Ou Yang, Tai Hsien, Porta-Pardo, Eduard, Gao, Galen F., Plaisier, Christopher L., Eddy, James A., Ziv, Elad, Culhane, Aedin C., Paull, Evan O., Sivakumar, I. K.Ashok, Gentles, Andrew J., Malhotra, Raunaq, Farshidfar, Farshad, Colaprico, Antonio, Parker, Joel S., Mose, Lisle E., Vo, Nam Sy, Liu, Jianfang, Liu, Yuexin, Rader, Janet, Dhankani, Varsha, Reynolds, Sheila M., Bowlby, Reanne, Califano, Andrea, Cherniack, Andrew D., Anastassiou, Dimitris, Bedognetti, Davide, Rao, Arvind, Chen, Ken, Krasnitz, Alexander, Hu, Hai, Malta, Tathiane M., Noushmehr, Houtan, Pedamallu, Chandra Sekhar, Bullman, Susan, Ojesina, Akinyemi I., Lamb, Andrew, Zhou, Wanding, Shen, Hui, Choueiri, Toni K., Weinstein, John N., Guinney, Justin, Saltz, Joel, Holt, Robert, Zhang, Jiashan (Julia), de Krijger, Ronald, The Cancer Genome Atlas Research Network, Onderzoeksgroep 6, Pathologie Pathologen staf, Thorsson, Vésteinn, Gibbs, David L., Brown, Scott D., Wolf, Denise, Bortone, Dante S., Ou Yang, Tai Hsien, Porta-Pardo, Eduard, Gao, Galen F., Plaisier, Christopher L., Eddy, James A., Ziv, Elad, Culhane, Aedin C., Paull, Evan O., Sivakumar, I. K.Ashok, Gentles, Andrew J., Malhotra, Raunaq, Farshidfar, Farshad, Colaprico, Antonio, Parker, Joel S., Mose, Lisle E., Vo, Nam Sy, Liu, Jianfang, Liu, Yuexin, Rader, Janet, Dhankani, Varsha, Reynolds, Sheila M., Bowlby, Reanne, Califano, Andrea, Cherniack, Andrew D., Anastassiou, Dimitris, Bedognetti, Davide, Rao, Arvind, Chen, Ken, Krasnitz, Alexander, Hu, Hai, Malta, Tathiane M., Noushmehr, Houtan, Pedamallu, Chandra Sekhar, Bullman, Susan, Ojesina, Akinyemi I., Lamb, Andrew, Zhou, Wanding, Shen, Hui, Choueiri, Toni K., Weinstein, John N., Guinney, Justin, Saltz, Joel, Holt, Robert, Zhang, Jiashan (Julia), de Krijger, Ronald, and The Cancer Genome Atlas Research Network

Published
2018

15. Comparative Molecular Analysis of Gastrointestinal Adenocarcinomas

Author

Pathologie Pathologen staf, Liu, Yang, Sethi, Nilay S, Hinoue, Toshinori, Schneider, Barbara G, Cherniack, Andrew D, Sanchez-Vega, Francisco, Seoane, Jose A, Farshidfar, Farshad, Bowlby, Reanne, Islam, Mirazul, Kim, Jaegil, Chatila, Walid, Akbani, Rehan, Kanchi, Rupa S, Rabkin, Charles S, Willis, Joseph E, Wang, Kenneth K, McCall, Shannon J, Mishra, Lopa, Ojesina, Akinyemi I, Bullman, Susan, Pedamallu, Chandra Sekhar, Lazar, Alexander J, Sakai, Ryo, Thorsson, Vésteinn, Bass, Adam J, Laird, Peter W, Cancer Genome Atlas Research Network, Pathologie Pathologen staf, Liu, Yang, Sethi, Nilay S, Hinoue, Toshinori, Schneider, Barbara G, Cherniack, Andrew D, Sanchez-Vega, Francisco, Seoane, Jose A, Farshidfar, Farshad, Bowlby, Reanne, Islam, Mirazul, Kim, Jaegil, Chatila, Walid, Akbani, Rehan, Kanchi, Rupa S, Rabkin, Charles S, Willis, Joseph E, Wang, Kenneth K, McCall, Shannon J, Mishra, Lopa, Ojesina, Akinyemi I, Bullman, Susan, Pedamallu, Chandra Sekhar, Lazar, Alexander J, Sakai, Ryo, Thorsson, Vésteinn, Bass, Adam J, Laird, Peter W, and Cancer Genome Atlas Research Network

Published
2018

16. Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH-Mutant Molecular Profiles - correction

Author

Farshidfar, Farshad, Zheng, Siyuan, Gingras, Marie-Claude, Newton, Yulia, Shih, Juliann, Robertson, A Gordon, Hinoue, Toshinori, Hoadley, Katherine A, Gibb, Ewan A, Roszik, Jason, Covington, Kyle R, Wu, Chia-Chin, Shinbrot, Eve, Stransky, Nicolas, Hegde, Apurva, Yang, Ju Dong, Reznik, Ed, Sadeghi, Sara, Pedamallu, Chandra Sekhar, Ojesina, Akinyemi I, Hess, Julian M, Auman, J Todd, Rhie, Suhn Kyong, Bowlby, Reanne, Borad, Mitesh J, Zhu, Andrew X, Stuart, Josh M, Sander, Chris, Akbani, Rehan, Cherniack, Andrew D, Deshpande, Vikram, Mounajjed, Taofic, Foo, Wai Chin, Torbenson, Michael S, Kleiner, David E, Laird, Peter W, Wheeler, David A, McRee, Autumn J, Bathe, Oliver F, Andersen, Jesper B, Bardeesy, Nabeel, Roberts, Lewis R, Kwong, Lawrence N, Farshidfar, Farshad, Zheng, Siyuan, Gingras, Marie-Claude, Newton, Yulia, Shih, Juliann, Robertson, A Gordon, Hinoue, Toshinori, Hoadley, Katherine A, Gibb, Ewan A, Roszik, Jason, Covington, Kyle R, Wu, Chia-Chin, Shinbrot, Eve, Stransky, Nicolas, Hegde, Apurva, Yang, Ju Dong, Reznik, Ed, Sadeghi, Sara, Pedamallu, Chandra Sekhar, Ojesina, Akinyemi I, Hess, Julian M, Auman, J Todd, Rhie, Suhn Kyong, Bowlby, Reanne, Borad, Mitesh J, Zhu, Andrew X, Stuart, Josh M, Sander, Chris, Akbani, Rehan, Cherniack, Andrew D, Deshpande, Vikram, Mounajjed, Taofic, Foo, Wai Chin, Torbenson, Michael S, Kleiner, David E, Laird, Peter W, Wheeler, David A, McRee, Autumn J, Bathe, Oliver F, Andersen, Jesper B, Bardeesy, Nabeel, Roberts, Lewis R, and Kwong, Lawrence N

Published
2017

17. Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH-Mutant Molecular Profiles

Author

Farshidfar, Farshad, Zheng, Siyuan, Gingras, Marie-Claude, Newton, Yulia, Shih, Juliann, Robertson, A Gordon, Hinoue, Toshinori, Hoadley, Katherine A, Gibb, Ewan A, Roszik, Jason, Covington, Kyle R, Wu, Chia-Chin, Shinbrot, Eve, Stransky, Nicolas, Hegde, Apurva, Yang, Ju Dong, Reznik, Ed, Sadeghi, Sara, Pedamallu, Chandra Sekhar, Ojesina, Akinyemi I, Hess, Julian M, Auman, J Todd, Rhie, Suhn Kyong, Bowlby, Reanne, Borad, Mitesh J, Zhu, Andrew X, Stuart, Josh M, Sander, Chris, Akbani, Rehan, Cherniack, Andrew D, Deshpande, Vikram, Mounajjed, Taofic, Foo, Wai Chin, Torbenson, Michael S, Kleiner, David E, Laird, Peter W, Wheeler, David A, McRee, Autumn J, Bathe, Oliver F, Andersen, Jesper B, Bardeesy, Nabeel, Roberts, Lewis R, Kwong, Lawrence N, Farshidfar, Farshad, Zheng, Siyuan, Gingras, Marie-Claude, Newton, Yulia, Shih, Juliann, Robertson, A Gordon, Hinoue, Toshinori, Hoadley, Katherine A, Gibb, Ewan A, Roszik, Jason, Covington, Kyle R, Wu, Chia-Chin, Shinbrot, Eve, Stransky, Nicolas, Hegde, Apurva, Yang, Ju Dong, Reznik, Ed, Sadeghi, Sara, Pedamallu, Chandra Sekhar, Ojesina, Akinyemi I, Hess, Julian M, Auman, J Todd, Rhie, Suhn Kyong, Bowlby, Reanne, Borad, Mitesh J, Zhu, Andrew X, Stuart, Josh M, Sander, Chris, Akbani, Rehan, Cherniack, Andrew D, Deshpande, Vikram, Mounajjed, Taofic, Foo, Wai Chin, Torbenson, Michael S, Kleiner, David E, Laird, Peter W, Wheeler, David A, McRee, Autumn J, Bathe, Oliver F, Andersen, Jesper B, Bardeesy, Nabeel, Roberts, Lewis R, and Kwong, Lawrence N

Abstract

Cholangiocarcinoma (CCA) is an aggressive malignancy of the bile ducts, with poor prognosis and limited treatment options. Here, we describe the integrated analysis of somatic mutations, RNA expression, copy number, and DNA methylation by The Cancer Genome Atlas of a set of predominantly intrahepatic CCA cases and propose a molecular classification scheme. We identified an IDH mutant-enriched subtype with distinct molecular features including low expression of chromatin modifiers, elevated expression of mitochondrial genes, and increased mitochondrial DNA copy number. Leveraging the multi-platform data, we observed that ARID1A exhibited DNA hypermethylation and decreased expression in the IDH mutant subtype. More broadly, we found that IDH mutations are associated with an expanded histological spectrum of liver tumors with molecular features that stratify with CCA. Our studies reveal insights into the molecular pathogenesis and heterogeneity of cholangiocarcinoma and provide classification information of potential therapeutic significance.

Published
2017

18. Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH-Mutant Molecular Profiles - correction

Author

Farshidfar, Farshad, Zheng, Siyuan, Gingras, Marie-Claude, Newton, Yulia, Shih, Juliann, Robertson, A Gordon, Hinoue, Toshinori, Hoadley, Katherine A, Gibb, Ewan A, Roszik, Jason, Covington, Kyle R, Wu, Chia-Chin, Shinbrot, Eve, Stransky, Nicolas, Hegde, Apurva, Yang, Ju Dong, Reznik, Ed, Sadeghi, Sara, Pedamallu, Chandra Sekhar, Ojesina, Akinyemi I, Hess, Julian M, Auman, J Todd, Rhie, Suhn Kyong, Bowlby, Reanne, Borad, Mitesh J, Zhu, Andrew X, Stuart, Josh M, Sander, Chris, Akbani, Rehan, Cherniack, Andrew D, Deshpande, Vikram, Mounajjed, Taofic, Foo, Wai Chin, Torbenson, Michael S, Kleiner, David E, Laird, Peter W, Wheeler, David A, McRee, Autumn J, Bathe, Oliver F, Andersen, Jesper B, Bardeesy, Nabeel, Roberts, Lewis R, Kwong, Lawrence N, Farshidfar, Farshad, Zheng, Siyuan, Gingras, Marie-Claude, Newton, Yulia, Shih, Juliann, Robertson, A Gordon, Hinoue, Toshinori, Hoadley, Katherine A, Gibb, Ewan A, Roszik, Jason, Covington, Kyle R, Wu, Chia-Chin, Shinbrot, Eve, Stransky, Nicolas, Hegde, Apurva, Yang, Ju Dong, Reznik, Ed, Sadeghi, Sara, Pedamallu, Chandra Sekhar, Ojesina, Akinyemi I, Hess, Julian M, Auman, J Todd, Rhie, Suhn Kyong, Bowlby, Reanne, Borad, Mitesh J, Zhu, Andrew X, Stuart, Josh M, Sander, Chris, Akbani, Rehan, Cherniack, Andrew D, Deshpande, Vikram, Mounajjed, Taofic, Foo, Wai Chin, Torbenson, Michael S, Kleiner, David E, Laird, Peter W, Wheeler, David A, McRee, Autumn J, Bathe, Oliver F, Andersen, Jesper B, Bardeesy, Nabeel, Roberts, Lewis R, and Kwong, Lawrence N

Published
2017

19. Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH-Mutant Molecular Profiles

Author

Farshidfar, Farshad, Zheng, Siyuan, Gingras, Marie-Claude, Newton, Yulia, Shih, Juliann, Robertson, A Gordon, Hinoue, Toshinori, Hoadley, Katherine A, Gibb, Ewan A, Roszik, Jason, Covington, Kyle R, Wu, Chia-Chin, Shinbrot, Eve, Stransky, Nicolas, Hegde, Apurva, Yang, Ju Dong, Reznik, Ed, Sadeghi, Sara, Pedamallu, Chandra Sekhar, Ojesina, Akinyemi I, Hess, Julian M, Auman, J Todd, Rhie, Suhn Kyong, Bowlby, Reanne, Borad, Mitesh J, Zhu, Andrew X, Stuart, Josh M, Sander, Chris, Akbani, Rehan, Cherniack, Andrew D, Deshpande, Vikram, Mounajjed, Taofic, Foo, Wai Chin, Torbenson, Michael S, Kleiner, David E, Laird, Peter W, Wheeler, David A, McRee, Autumn J, Bathe, Oliver F, Andersen, Jesper B, Bardeesy, Nabeel, Roberts, Lewis R, Kwong, Lawrence N, Farshidfar, Farshad, Zheng, Siyuan, Gingras, Marie-Claude, Newton, Yulia, Shih, Juliann, Robertson, A Gordon, Hinoue, Toshinori, Hoadley, Katherine A, Gibb, Ewan A, Roszik, Jason, Covington, Kyle R, Wu, Chia-Chin, Shinbrot, Eve, Stransky, Nicolas, Hegde, Apurva, Yang, Ju Dong, Reznik, Ed, Sadeghi, Sara, Pedamallu, Chandra Sekhar, Ojesina, Akinyemi I, Hess, Julian M, Auman, J Todd, Rhie, Suhn Kyong, Bowlby, Reanne, Borad, Mitesh J, Zhu, Andrew X, Stuart, Josh M, Sander, Chris, Akbani, Rehan, Cherniack, Andrew D, Deshpande, Vikram, Mounajjed, Taofic, Foo, Wai Chin, Torbenson, Michael S, Kleiner, David E, Laird, Peter W, Wheeler, David A, McRee, Autumn J, Bathe, Oliver F, Andersen, Jesper B, Bardeesy, Nabeel, Roberts, Lewis R, and Kwong, Lawrence N

Abstract

Cholangiocarcinoma (CCA) is an aggressive malignancy of the bile ducts, with poor prognosis and limited treatment options. Here, we describe the integrated analysis of somatic mutations, RNA expression, copy number, and DNA methylation by The Cancer Genome Atlas of a set of predominantly intrahepatic CCA cases and propose a molecular classification scheme. We identified an IDH mutant-enriched subtype with distinct molecular features including low expression of chromatin modifiers, elevated expression of mitochondrial genes, and increased mitochondrial DNA copy number. Leveraging the multi-platform data, we observed that ARID1A exhibited DNA hypermethylation and decreased expression in the IDH mutant subtype. More broadly, we found that IDH mutations are associated with an expanded histological spectrum of liver tumors with molecular features that stratify with CCA. Our studies reveal insights into the molecular pathogenesis and heterogeneity of cholangiocarcinoma and provide classification information of potential therapeutic significance.

Published
2017

20. Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH-Mutant Molecular Profiles

Author

Roberts, Lewis R, Roberts, Lewis R, Farshidfar, Farshad, Zheng, Siyuan, Gingras, Marie-Claude, Newton, Yulia, Shih, Juliann, Robertson, A Gordon, Hinoue, Toshinori, Hoadley, Katherine A, Gibbs, Richard, Roszik, Jason, Covington, Kyle, Wu, Chia-Chin, Shinbrot, Eve, Stransky, Nicolas, Hegde, Apurva M, Yang, Ju Dong, Reznik, Ed, Sadeghi, Sara, Pedamallu, Chandra Sekhar, Ojesina, Akinyemi I, Hess, Julian, Auman, J Todd, Rhie, Suhn K, Bowlby, Reanne, Borad, Mitesh J, Stuart, Josh, Sander, Chris, Akbani, Rehan, Cherniack, Andrew D, Laird, Peter W, Deshpande, Vikram, Mounajjed, Taofic, Foo, Wai Chin, Torbenson, Michael, Kleiner, David E, Wheeler, David A, Mcree, Autumn J, Bathe, Oliver F, Andersen, Jesper B, Bardeesy, Nabeel, Kwong, Lawrence N, Roberts, Lewis R, Roberts, Lewis R, Farshidfar, Farshad, Zheng, Siyuan, Gingras, Marie-Claude, Newton, Yulia, Shih, Juliann, Robertson, A Gordon, Hinoue, Toshinori, Hoadley, Katherine A, Gibbs, Richard, Roszik, Jason, Covington, Kyle, Wu, Chia-Chin, Shinbrot, Eve, Stransky, Nicolas, Hegde, Apurva M, Yang, Ju Dong, Reznik, Ed, Sadeghi, Sara, Pedamallu, Chandra Sekhar, Ojesina, Akinyemi I, Hess, Julian, Auman, J Todd, Rhie, Suhn K, Bowlby, Reanne, Borad, Mitesh J, Stuart, Josh, Sander, Chris, Akbani, Rehan, Cherniack, Andrew D, Laird, Peter W, Deshpande, Vikram, Mounajjed, Taofic, Foo, Wai Chin, Torbenson, Michael, Kleiner, David E, Wheeler, David A, Mcree, Autumn J, Bathe, Oliver F, Andersen, Jesper B, Bardeesy, Nabeel, and Kwong, Lawrence N

Published
2016

21. Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH-Mutant Molecular Profiles

Author

Roberts, Lewis R, Roberts, Lewis R, Farshidfar, Farshad, Zheng, Siyuan, Gingras, Marie-Claude, Newton, Yulia, Shih, Juliann, Robertson, A Gordon, Hinoue, Toshinori, Hoadley, Katherine A, Gibbs, Richard, Roszik, Jason, Covington, Kyle, Wu, Chia-Chin, Shinbrot, Eve, Stransky, Nicolas, Hegde, Apurva M, Yang, Ju Dong, Reznik, Ed, Sadeghi, Sara, Pedamallu, Chandra Sekhar, Ojesina, Akinyemi I, Hess, Julian, Auman, J Todd, Rhie, Suhn K, Bowlby, Reanne, Borad, Mitesh J, Stuart, Josh, Sander, Chris, Akbani, Rehan, Cherniack, Andrew D, Laird, Peter W, Deshpande, Vikram, Mounajjed, Taofic, Foo, Wai Chin, Torbenson, Michael, Kleiner, David E, Wheeler, David A, Mcree, Autumn J, Bathe, Oliver F, Andersen, Jesper B, Bardeesy, Nabeel, Kwong, Lawrence N, Roberts, Lewis R, Roberts, Lewis R, Farshidfar, Farshad, Zheng, Siyuan, Gingras, Marie-Claude, Newton, Yulia, Shih, Juliann, Robertson, A Gordon, Hinoue, Toshinori, Hoadley, Katherine A, Gibbs, Richard, Roszik, Jason, Covington, Kyle, Wu, Chia-Chin, Shinbrot, Eve, Stransky, Nicolas, Hegde, Apurva M, Yang, Ju Dong, Reznik, Ed, Sadeghi, Sara, Pedamallu, Chandra Sekhar, Ojesina, Akinyemi I, Hess, Julian, Auman, J Todd, Rhie, Suhn K, Bowlby, Reanne, Borad, Mitesh J, Stuart, Josh, Sander, Chris, Akbani, Rehan, Cherniack, Andrew D, Laird, Peter W, Deshpande, Vikram, Mounajjed, Taofic, Foo, Wai Chin, Torbenson, Michael, Kleiner, David E, Wheeler, David A, Mcree, Autumn J, Bathe, Oliver F, Andersen, Jesper B, Bardeesy, Nabeel, and Kwong, Lawrence N

Published
2016

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