NRL and CRX Define Photoreceptor Identity and Reveal Subgroup-Specific Dependencies in Medulloblastoma

被引：47

作者：

Garancher, Alexandra ^{[1
,2
,3
,4
,5
]}

Lin, Charles Y. ^{[17
]}

Morabito, Morgane ^{[1
,2
,3
,4
,5
]}

Richer, Wilfrid ^{[5
,6
,7
,8
]}

Rocques, Nathalie ^{[1
,2
,3
,4
,5
]}

Larcher, Magalie ^{[1
,2
,3
,4
,5
]}

Bihannic, Laure ^{[1
,2
,3
,4
,5
,9
]}

Smith, Kyle ^{[9
]}

Miquel, Catherine ^{[10
,11
]}

Leboucher, Sophie ^{[1
]}

Herath, Nirmitha I. ^{[1
,2
,3
,4
,5
]}

Dupuy, Fanny ^{[1
,2
,3
,4
,5
,19
]}

Varlet, Pascale ^{[11
,18
]}

Haberler, Christine ^{[12
]}

Walczak, Christine ^{[1
,4
,5
,13
]}

El Tayara, Nadine ^{[1
,4
,5
,13
]}

Volk, Andreas ^{[1
,4
,5
,13
]}

Puget, Stephanie ^{[11
,14
]}

Doz, Francois ^{[6
,11
,15
]}

Delattre, Olivier ^{[5
,6
,7
,15
]}

Druillennec, Sabine ^{[1
,2
,3
,4
,5
]}

Ayrault, Olivier ^{[1
,2
,3
,4
,5
]}

Wechsler-Reya, Robert J. ^{[16
]}

Eychene, Alain ^{[1
,2
,3
,4
,5
]}

Bourdeaut, Franck ^{[5
,6
,7
,8
,15
]}

Northcott, Paul A. ^{[9
]}

Pouponnot, Celio ^{[1
,2
,3
,4
,5
]}

机构：

[1] Ctr Univ Orsay, Inst Curie Rech, Lab 110, F-91405 Orsay, France

[2] Ctr Univ Orsay, INSERM U1021, F-91405 Orsay, France

[3] Ctr Univ Orsay, CNRS UMR 3347, F-91405 Orsay, France

[4] Univ Paris Sud 11, F-91405 Orsay, France

[5] PSL Res Univ, Paris, France

[6] Inst Curie, F-75248 Paris, France

[7] INSERM, U830, F-75248 Paris, France

[8] Inst Curie SiRIC, Translat Res Pediat Oncol, Paris, France

[9] St Jude Childrens Res Hosp, Dept Dev Neurobiol, 262 Danny Thomas Pl,MS325, Memphis, TN 38017 USA

[10] Univ Paris Diderot, Dept Neuropathol, Hop St Anne, Sorbonne Paris Cite,INSERM UMR S1165, Paris, France

[11] Univ Paris Diderot, Sorbonne Paris Cite, Paris, France

[12] Med Univ Vienna, Inst Neurol, Vienna, Austria

[13] Ctr Univ Orsay, CNRS, INSERM U1196, F-91405 Orsay, France

[14] Hop Necker Enfants Malad, AP HP, Dept Neurochirurg Pediat, Paris, France

[15] Inst Curie, SIREDO Ctr Care Innovat Res Pediat Adolescent & Y, Paris, France

[16] Sanford Burnham Prebys Med Discovery Inst, Tumor Initiat & Maintenance Program, NCI Designated Canc Ctr, La Jolla, CA 92037 USA

[17] Baylor Coll Med, Dept Mol & Human Genet, 1 Baylor Pl, Houston, TX 77030 USA

[18] Univ Paris Diderot, Dept Neuropathol, Hop St Anne, Sorbonne Paris Cite,INSERM U894, Paris, France

[19] McGill Univ, Dept Biochem, Goodman Canc Res Ctr, Montreal, PQ, Canada

来源：

CANCER CELL | 2018年 / 33卷 / 03期

关键词：

TRANSCRIPTIONAL REGULATION; LEUCINE-ZIPPER; MAF; DIFFERENTIATION; RETINA; CELLS; EXPRESSION; LANDSCAPE; MECHANISM; APOPTOSIS;

D O I：

10.1016/j.ccell.2018.02.006

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Cancer cells often express differentiation programs unrelated to their tissue of origin, although the contribution of these aberrant phenotypes to malignancy is poorly understood. An aggressive subgroup of medulloblastoma, a malignant pediatric brain tumor of the cerebellum, expresses a photoreceptor differentiation program normally expressed in the retina. We establish that two photoreceptor-specific transcription factors, NRL and CRX, are master regulators of this program and are required for tumor maintenance in this subgroup. Beyond photoreceptor lineage genes, we identify BCL-XL as a key transcriptional target of NRL and provide evidence substantiating anti-BCL therapy as a rational treatment opportunity for select MB patients. Our results highlight the utility of studying aberrant differentiation programs in cancer and their potential as selective therapeutic vulnerabilities.

引用

页码：435 / +

页数：21

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