SRF-FOXO1 and SRF-NCOA1 Fusion Genes Delineate a Distinctive Subset of Well-differentiated Rhabdomyosarcoma.
Biomarkers, Tumor
/ genetics
Cell Differentiation
Child, Preschool
Comparative Genomic Hybridization
Female
Forkhead Box Protein O1
/ genetics
Gene Fusion
Genetic Predisposition to Disease
Head and Neck Neoplasms
/ classification
Humans
In Situ Hybridization, Fluorescence
Infant
Male
Neck Muscles
/ pathology
Nuclear Receptor Coactivator 1
/ genetics
Paraspinal Muscles
/ pathology
Phenotype
Rhabdomyosarcoma
/ classification
Sequence Analysis, RNA
Serum Response Factor
/ genetics
Treatment Outcome
Journal
The American journal of surgical pathology
ISSN: 1532-0979
Titre abrégé: Am J Surg Pathol
Pays: United States
ID NLM: 7707904
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
pubmed:
19
3
2020
medline:
29
7
2020
entrez:
19
3
2020
Statut:
ppublish
Résumé
Rhabdomyosarcoma (RMS) encompasses a heterogenous collection of tumors in which new groups have recently been identified that improved the World Health Organization (WHO) classification. While performing RNA-sequencing in our routine practice, we identified 3 cases of well-differentiated RMS harboring new fusion genes. We also analyzed these tumors through array-comparative genomic hybridization. Clinically, these tumors were deep paraspinal tumors, occurring in neo-nat and young children. The patients underwent resection and adjuvant therapy. At the time of last follow-up (ranging from 12 to 108 mo), they were alive without disease. Histologically, these tumors consisted of well-differentiated rhabdomyoblastic proliferations with nuclear atypia, infiltrative borders, and a specific growth pattern. These tumors harbored new fusion genes involving SRF and either FOXO1 or NCOA1. We compared the expression profiles of these 3 tumors to the expression data of a series of 33 skeletal muscle tumors including embryonal RMSs, alveolar rhandomyosarcomas, RMSs with VGLL2 fusions, RMSs with the myoD1 mutation, EWSR1/FUS-TFCP2 epithelioid and spindle cell RMSs of the bone, and rhabdomyomas with PTCH1 loss. According to clustering analyses, the 3 SRF-fused tumors formed a distinct group with a specific expression profile different from that of the other types of skeletal muscle tumors. Array-comparative genomic hybridization showed a recurrent gain of chromosome 11. These 3 tumors define a new group of RMS associated with a fusion of the SRF gene. FOXO1 rearrangements, usually used to confirm the diagnosis of alveolar RMS and identify poor-outcome RMSs, were identified in a nonalveolar RMS for the first time.
Identifiants
pubmed: 32187044
doi: 10.1097/PAS.0000000000001464
pii: 00000478-202005000-00004
doi:
Substances chimiques
Biomarkers, Tumor
0
FOXO1 protein, human
0
Forkhead Box Protein O1
0
SRF protein, human
0
Serum Response Factor
0
NCOA1 protein, human
EC 2.3.1.48
Nuclear Receptor Coactivator 1
EC 2.3.1.48
Types de publication
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
607-616Références
Fletcher C, Bridge J, Hogendoorn P, et al. WHO Classification of Tumors of Soft Tissue and Bone, 4th edition. Lyon, France: IARC; 2013.
Mosquera JM, Sboner A, Zhang L, et al. Recurrent NCOA2 gene rearrangements in congenital/infantile spindle cell rhabdomyosarcoma. Genes Chromosomes Cancer. 2013;52:538–550.
Alaggio R, Zhang L, Sung Y-S, et al. A molecular study of pediatric spindle and sclerosing rhabdomyosarcoma: identification of novel and recurrent VGLL2-related fusions in infantile cases. Am J Surg Pathol. 2016;40:224–235.
Watson S, Perrin V, Guillemot D, et al. Transcriptomic definition of molecular subgroups of small round cell sarcomas. J Pathol. 2018;245:29–40.
Agaram NP, Chen C-L, Zhang L, et al. Recurrent MYOD1 mutations in pediatric and adult sclerosing and spindle cell rhabdomyosarcomas: evidence for a common pathogenesis. Genes Chromosomes Cancer. 2014;53:779–787.
Kohsaka S, Shukla N, Ameur N, et al. A recurrent neomorphic mutation in MYOD1 defines a clinically aggressive subset of embryonal rhabdomyosarcoma associated with PI3K-AKT pathway mutations. Nat Genet. 2014;46:595–600.
Rekhi B, Upadhyay P, Ramteke MP, et al. MYOD1 (L122R) mutations are associated with spindle cell and sclerosing rhabdomyosarcomas with aggressive clinical outcomes. Mod Pathol. 2016;29:1532–1540.
Agaram NP, LaQuaglia MP, Alaggio R, et al. MYOD1-mutant spindle cell and sclerosing rhabdomyosarcoma: an aggressive subtype irrespective of age. A reappraisal for molecular classification and risk stratification. Mod Pathol. 2019;32:27–36.
Le Loarer F, Cleven AHG, Bouvier C, et al. A subset of epithelioid and spindle cell rhabdomyosarcomas is associated with TFCP2 fusions and common ALK upregulation. Mod Pathol. 2019;33:404–419.
Agaram NP, Zhang L, Sung Y-S, et al. Expanding the spectrum of intraosseous rhabdomyosarcoma: correlation between 2 distinct gene fusions and phenotype. Am J Surg Pathol. 2019;43:695–702.
Martinez AP, Fritchie KJ, Weiss SW, et al. Histiocyte-rich rhabdomyoblastic tumor: rhabdomyosarcoma, rhabdomyoma, or rhabdomyoblastic tumor of uncertain malignant potential? A histologically distinctive rhabdomyoblastic tumor in search of a place in the classification of skeletal muscle neoplasms. Mod Pathol. 2019;32:446–457.
Ge H, Liu K, Juan T, et al. FusionMap: detecting fusion genes from next-generation sequencing data at base-pair resolution. Bioinformatics. 2011;27:1922–1928.
Haas B, Dobin A, Stransky N, et al. STAR-Fusion: fast and accurate fusion transcript detection from RNA-Seq. BioRxiv. 2017:120295.
Nicorici DS, Edgren H, Kangaspeska S, et al. FusionCatcher—a tool for finding somatic fusion genes in paired-end RNA-sequencing data. BioRxiv. 2014:011650.
Benelli M, Pescucci C, Marseglia G, et al. Discovering chimeric transcripts in paired-end RNA-seq data by using EricScript. Bioinformatics. 2012;28:3232–3239.
Bray NL, Pimentel H, Melsted P, et al. Near-optimal probabilistic RNA-seq quantification. Nat Biotechnol. 2016;34:525–527.
R Development Core Team. R: A Language and Environment for Statistical Computing. Vienna, Austria: R Foundation for Statistical Computing; 2017.
Subramanian A, Tamayo P, Mootha VK, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA. 2005;102:15545–15550.
Laé M, Ahn EH, Mercado GE, et al. Global gene expression profiling of PAX-FKHR fusion-positive alveolar and PAX-FKHR fusion-negative embryonal rhabdomyosarcomas. J Pathol. 2007;212:143–151.
Williamson D, Missiaglia E, de Reyniès A, et al. Fusion gene-negative alveolar rhabdomyosarcoma is clinically and molecularly indistinguishable from embryonal rhabdomyosarcoma. J Clin Oncol. 2010;28:2151–2158.
Choi GC, Li J, Wang Y, et al. The metalloprotease ADAMTS8 displays antitumor properties through antagonizing EGFR–MEK–ERK signaling and is silenced in carcinomas by CpG methylation. Mol Cancer Res. 2014;12:228–238.
Urbini M, Astolfi A, Indio V, et al. Identification of SRF-E2F1 fusion transcript in EWSR-negative myoepithelioma of the soft tissue. Oncotarget. 2017;8:60036–60045.
Pipes GCT, Creemers EE, Olson EN. The myocardin family of transcriptional coactivators: versatile regulators of cell growth, migration, and myogenesis. Genes Dev. 2006;20:1545–1556.
Coletti D, Daou N, Hassani M, et al. Serum response factor in muscle tissues: from development to ageing. Eur J Transl Myol. 2016;26:6008.
Li S, Czubryt MP, McAnally J, et al. Requirement for serum response factor for skeletal muscle growth and maturation revealed by tissue-specific gene deletion in mice. Proc Natl Acad Sci USA. 2005;102:1082–1087.
Wachtel M, Dettling M, Koscielniak E, et al. Gene expression signatures identify rhabdomyosarcoma subtypes and detect a novel t(2;2)(q35;p23) translocation fusing PAX3 to NCOA1. Cancer Res. 2004;64:5539–5545.
Sumegi J, Streblow R, Frayer RW, et al. Recurrent t(2;2) and t(2;8) translocations in rhabdomyosarcoma without the canonical PAX-FOXO1 fuse PAX3 to members of the nuclear receptor transcriptional coactivator family. Genes Chromosomes Cancer. 2010;49:224–236.
Huang S-C, Ghossein RA, Bishop JA, et al. Novel PAX3-NCOA1 fusions in biphenotypic sinonasal sarcoma with focal rhabdomyoblastic differentiation. Am J Surg Pathol. 2016;40:51–59.
Andreasen S, Bishop JA, Hellquist H, et al. Biphenotypic sinonasal sarcoma: demographics, clinicopathological characteristics, molecular features, and prognosis of a recently described entity. Virchows Arch. 2018;473:615–626.
Leo C, Chen JD. The SRC family of nuclear receptor coactivators. Gene. 2000;245:1–11.
Xu J, Wu R-C, O’Malley BW. Normal and cancer-related functions of the p160 steroid receptor co-activator (SRC) family. Nat Rev Cancer. 2009;9:615–630.
Xu J, Li Q. Review of the in vivo functions of the p160 steroid receptor coactivator family. Mol Endocrinol. 2003;17:1681–1692.
Douglass EC, Valentine M, Etcubanas E, et al. A specific chromosomal abnormality in rhabdomyosarcoma. Cytogenet Cell Genet. 1987;45:148–155.
Turc-Carel C, Lizard-Nacol S, Justrabo E, et al. Consistent chromosomal translocation in alveolar rhabdomyosarcoma. Cancer Genet Cytogenet. 1986;19:361–362.
Wang-Wuu S, Soukup S, Ballard E, et al. Chromosomal analysis of sixteen human rhabdomyosarcomas. Cancer Res. 1988;48:983–987.
Barr FG. Gene fusions involving PAX and FOX family members in alveolar rhabdomyosarcoma. Oncogene. 2001;20:5736–5746.
Xu M, Chen X, Chen D, et al. FoxO1: a novel insight into its molecular mechanisms in the regulation of skeletal muscle differentiation and fiber type specification. Oncotarget. 2017;8:10662–10674.