Molecular subgroups of atypical teratoid rhabdoid tumours in children: an integrated genomic and clinicopathological analysis

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Fältnamn	Indikatorer	Metadata
000		06335naa a2201129 4500
001		oai:DiVA.org:uu-255273
003		SwePub
008		150615s2015 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
024	7	a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-2552732 URI
024	7	a https://doi.org/10.1016/S1470-2045(15)70114-22 DOI
040		a (SwePub)uu
041		a engb eng
042		9 SwePub
072	7	a ref2 swepub-contenttype
072	7	a art2 swepub-publicationtype
100	1	a Torchia, Jonathon4 aut
245	1 0	a Molecular subgroups of atypical teratoid rhabdoid tumours in children :b an integrated genomic and clinicopathological analysis
264	1	c 2015
338		a print2 rdacarrier
520		a Background Rhabdoid brain tumours, also called atypical teratoid rhabdoid tumours, are lethal childhood cancers with characteristic genetic alterations of SMARCB1/hSNF5. Lack of biological understanding of the substantial clinical heterogeneity of these tumours restricts therapeutic advances. We integrated genomic and clinicopathological analyses of a cohort of patients with atypical teratoid rhabdoid tumours to find out the molecular basis for clinical heterogeneity in these tumours. Methods We obtained 259 rhabdoid tumours from 37 international institutions and assessed transcriptional profiles in 43 primary tumours and copy number profiles in 38 primary tumours to discover molecular subgroups of atypical teratoid rhabdoid tumours. We used gene and pathway enrichment analyses to discover group-specific molecular markers and did immunohistochemical analyses on 125 primary tumours to evaluate clinicopathological significance of molecular subgroup and ASCL1-NOTCH signalling. Findings Transcriptional analyses identified two atypical teratoid rhabdoid tumour subgroups with differential enrichment of genetic pathways, and distinct clinicopathological and survival features. Expression of ASCL1, a regulator of NOTCH signalling, correlated with supratentorial location (p=0.004) and superior 5-year overall survival (35%, 95% CI 13-57, and 20%, 6-34, for ASCL1-positive and ASCL1-negative tumours, respectively; p=0.033) in 70 patients who received multimodal treatment. ASCL1 expression also correlated with superior 5-year overall survival (34%, 7-61, and 9%, 0-21, for ASCL1-positive and ASCL1-negative tumours, respectively; p=0.001) in 39 patients who received only chemotherapy without radiation. Cox hazard ratios for overall survival in patients with differential ASCL1 enrichment treated with chemotherapy with or without radiation were 2.02 (95% CI 1.04-3.85; p=0.038) and 3.98 (1.71-9.26; p=0.001). Integrated analyses of molecular subgroupings with clinical prognostic factors showed three distinct clinical risk groups of tumours with different therapeutic outcomes. Interpretation An integration of clinical risk factors and tumour molecular groups can be used to identify patients who are likely to have improved long-term radiation-free survival and might help therapeutic stratification of patients with atypical teratoid rhabdoid tumours.
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Cancer och onkologi0 (SwePub)302032 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Cancer and Oncology0 (SwePub)302032 hsv//eng
700	1	a Picard, Daniel4 aut
700	1	a Lafay-Cousin, Lucie4 aut
700	1	a Hawkins, Cynthia E.4 aut
700	1	a Kim, Seung-Ki4 aut
700	1	a Letourneau, Louis4 aut
700	1	a Ra, Young-Shin4 aut
700	1	a Ho, King Ching4 aut
700	1	a Chan, Tiffany Sin Yu4 aut
700	1	a Sin-Chan, Patrick4 aut
700	1	a Dunham, Christopher P.4 aut
700	1	a Yip, Stephen4 aut
700	1	a Ng, Ho-Keung4 aut
700	1	a Lu, Jian-Qiang4 aut
700	1	a Albrecht, Steffen4 aut
700	1	a Pimentel, Jose4 aut
700	1	a Chan, Jennifer A.4 aut
700	1	a Somers, Gino R.4 aut
700	1	a Zielenska, Maria4 aut
700	1	a Faria, Claudia C.4 aut
700	1	a Roque, Lucia4 aut
700	1	a Baskin, Berivanu Uppsala universitet,Medicinsk genetik och genomik4 aut0 (Swepub:uu)berba972
700	1	a Birks, Diane4 aut
700	1	a Foreman, Nick4 aut
700	1	a Strother, Douglas4 aut
700	1	a Klekner, Almos4 aut
700	1	a Garami, Miklos4 aut
700	1	a Hauser, Peter4 aut
700	1	a Hortobagyi, Tibor4 aut
700	1	a Bognar, Laszlo4 aut
700	1	a Wilson, Beverly4 aut
700	1	a Hukin, Juliette4 aut
700	1	a Carret, Anne-Sophie4 aut
700	1	a Van Meter, Timothy E.4 aut
700	1	a Nakamura, Hideo4 aut
700	1	a Toledano, Helen4 aut
700	1	a Fried, Iris4 aut
700	1	a Fults, Daniel4 aut
700	1	a Wataya, Takafumi4 aut
700	1	a Fryer, Chris4 aut
700	1	a Eisenstat, David D.4 aut
700	1	a Scheineman, Katrin4 aut
700	1	a Johnston, Donna4 aut
700	1	a Michaud, Jean4 aut
700	1	a Zelcer, Shayna4 aut
700	1	a Hammond, Robert4 aut
700	1	a Ramsay, David A.4 aut
700	1	a Fleming, Adam J.4 aut
700	1	a Lulla, Rishi R.4 aut
700	1	a Fangusaro, Jason R.4 aut
700	1	a Sirachainan, Nongnuch4 aut
700	1	a Larbcharoensub, Noppadol4 aut
700	1	a Hongeng, Suradej4 aut
700	1	a Barakzai, Muhammad Abrar4 aut
700	1	a Montpetit, Alexandre4 aut
700	1	a Stephens, Derek4 aut
700	1	a Grundy, Richard G.4 aut
700	1	a Schueller, Ulrich4 aut
700	1	a Nicolaides, Theodore4 aut
700	1	a Tihan, Tarik4 aut
700	1	a Phillips, Joanna4 aut
700	1	a Taylor, Michael D.4 aut
700	1	a Rutka, James T.4 aut
700	1	a Dirks, Peter4 aut
700	1	a Bader, Gary D.4 aut
700	1	a Warmuth-Metz, Monika4 aut
700	1	a Rutkowski, Stefan4 aut
700	1	a Pietsch, Torsten4 aut
700	1	a Judkins, Alexander R.4 aut
700	1	a Jabado, Nada4 aut
700	1	a Bouffet, Eric4 aut
700	1	a Huang, Annie4 aut
710	2	a Uppsala universitetb Medicinsk genetik och genomik4 org
773	0	t The Lancet Oncologyg 16:5, s. 569-582q 16:5<569-582x 1470-2045x 1474-5488
856	4 8	u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-255273
856	4 8	u https://doi.org/10.1016/S1470-2045(15)70114-2

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Av författaren/redakt...: Torchia, Jonatho ...; Picard, Daniel; Lafay-Cousin, Lu ...; Hawkins, Cynthia ...; Kim, Seung-Ki; Letourneau, Loui ...; visa fler...; Ra, Young-Shin; Ho, King Ching; Chan, Tiffany Si ...; Sin-Chan, Patric ...; Dunham, Christop ...; Yip, Stephen; Ng, Ho-Keung; Lu, Jian-Qiang; Albrecht, Steffe ...; Pimentel, Jose; Chan, Jennifer A ...; Somers, Gino R.; Zielenska, Maria; Faria, Claudia C ...; Roque, Lucia; Baskin, Berivan; Birks, Diane; Foreman, Nick; Strother, Dougla ...; Klekner, Almos; Garami, Miklos; Hauser, Peter; Hortobagyi, Tibo ...; Bognar, Laszlo; Wilson, Beverly; Hukin, Juliette; Carret, Anne-Sop ...; Van Meter, Timot ...; Nakamura, Hideo; Toledano, Helen; Fried, Iris; Fults, Daniel; Wataya, Takafumi; Fryer, Chris; Eisenstat, David ...; Scheineman, Katr ...; Johnston, Donna; Michaud, Jean; Zelcer, Shayna; Hammond, Robert; Ramsay, David A.; Fleming, Adam J.; Lulla, Rishi R.; Fangusaro, Jason ...; Sirachainan, Non ...; Larbcharoensub, ...; Hongeng, Suradej; Barakzai, Muhamm ...; Montpetit, Alexa ...; Stephens, Derek; Grundy, Richard ...; Schueller, Ulric ...; Nicolaides, Theo ...; Tihan, Tarik; Phillips, Joanna; Taylor, Michael ...; Rutka, James T.; Dirks, Peter; Bader, Gary D.; Warmuth-Metz, Mo ...; Rutkowski, Stefa ...; Pietsch, Torsten; Judkins, Alexand ...; Jabado, Nada; Bouffet, Eric; Huang, Annie; visa färre...

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