Idioma:

Genetic characterisation of adult primary pleomorphic uterine rhabdomyosarcoma and comparison with uterine carcinosarcoma

Ashley, Charles W ; Da Cruz Paula, Arnaud ; Ferrando, Lorenzo ; Gularte‐Mérida, Rodrigo ; Sebastiao, Ana P M ; Brown, David N ; Gazzo, Andrea M ; Pareja, Fresia ; Stylianou, Anthe ; Abu‐Rustum, Nadeem R ; Reis‐Filho, Jorge S ; Buehler, Darya ; Weisman, Paul ; Chiang, Sarah ; Weigelt, Britta

Histopathology, 2021-08, Vol.79 (2), p.176-186 [Periódico revisado por pares]

England: Wiley Subscription Services, Inc

Texto completo disponível

Citações Citado por

Enviar para

Título:
Genetic characterisation of adult primary pleomorphic uterine rhabdomyosarcoma and comparison with uterine carcinosarcoma
Autor: Ashley, Charles W ; Da Cruz Paula, Arnaud ; Ferrando, Lorenzo ; Gularte‐Mérida, Rodrigo ; Sebastiao, Ana P M ; Brown, David N ; Gazzo, Andrea M ; Pareja, Fresia ; Stylianou, Anthe ; Abu‐Rustum, Nadeem R ; Reis‐Filho, Jorge S ; Buehler, Darya ; Weisman, Paul ; Chiang, Sarah ; Weigelt, Britta
Assuntos: Adult ; carcinosarcoma ; Carcinosarcoma - genetics ; Carcinosarcoma - pathology ; Cdc4 protein ; Cluster Analysis ; Copy number ; Cytokeratin ; DNA Copy Number Variations ; Female ; Fibroblast growth factor receptor 1 ; fusion gene ; Gene Amplification ; Gene deletion ; Gene Fusion ; Genes, p53 - genetics ; Genomic Instability ; High-Throughput Nucleotide Sequencing ; Humans ; MDM2 protein ; molecular genetics ; Mutation ; p53 Protein ; Reclassification ; Rhabdomyosarcoma ; Rhabdomyosarcoma - genetics ; Rhabdomyosarcoma - pathology ; Sequence Analysis, DNA ; Sequence Analysis, RNA ; Tumors ; Uterine Neoplasms - genetics ; Uterine Neoplasms - pathology ; uterine rhabdomyosarcoma ; Uterus
É parte de: Histopathology, 2021-08, Vol.79 (2), p.176-186
Notas: S.C. and B.W. jointly supervised this work.
C.W.S. and A.D.C.P. contributed equally to this work.
ObjectType-Article-2
SourceType-Scholarly Journals-1
ObjectType-Feature-1
content type line 23
Authors’ Contributions
Joint supervision
B. Weigelt and S. Chiang supervised the study. S. Chiang conducted pathology review. C.W. Ashley, A. Da Cruz Paula, A.P.M. Sebastiao, F. Pareja and A. Stylianou performed sample processing and experiments. A. Da Cruz Paula, L. Ferrando, R. Gularte-Mérida and D.N. Brown performed bioinformatics analyses. Data analysis and interpretation was performed by C.W. Ashley, A. Da Cruz Paula, L. Ferrando, R.J. Gularte-Mérida, D.N. Brown, N.R. Abu-Rustum, J.S. Reis-Filho, D. Buehler, P. Weisman, S. Chiang and B. Weigelt. C.W. Ashley, A. Da Cruz Paula, S. Chiang and B. Weigelt drafted the manuscript, and all authors edited and approved the final draft of the manuscript.
Equal contribution
Descrição: Aims To characterise the genetic alterations in adult primary uterine rhabdomyosarcomas (uRMSs) and to investigate whether these tumours are genetically distinct from uterine carcinosarcomas (UCSs). Methods and results Three tumours originally diagnosed as primary adult pleomorphic uRMS were subjected to massively parallel sequencing targeting 468 cancer‐related genes and RNA‐sequencing. Mutational profiles were compared with those of UCSs (n = 57) obtained from The Cancer Genome Atlas. Sequencing data analyses were performed using validated bioinformatic approaches. Pathogenic TP53 mutations and high levels of genomic instability were detected in the three cases. uRMS1 harboured a likely pathogenic YTHDF2–FOXR1 fusion. uRMS2 harboured a PPP2R1A hotspot mutation and amplification of multiple genes, including WHSC1L1, FGFR1, MDM2, and CCNE1, whereas uRMS3 harboured an FBXW7 hotspot mutation and an ANKRD11 homozygous deletion. Hierarchical clustering of somatic mutations and copy number alterations revealed that these tumours initially diagnosed as pleomorphic uRMSs and UCSs were similar. Subsequent comprehensive pathological re‐review of the three uRMSs revealed previously unidentified minute pan‐cytokeratin‐positive atypical glands in one case (uRMS3), favouring its reclassification as UCS with extensive rhabdomyosarcomatous overgrowth. Conclusions Adult pleomorphic uRMSs harbour TP53 mutations and high levels of copy number alterations. Our findings underscore the challenge in discriminating between uRMS and UCS with rhabdomyosarcomatous differentiation.
Editor: England: Wiley Subscription Services, Inc
Idioma: Inglês

Links

View this record in MEDLINE/PubMed

Voltar para lista de resultados

Realização: Logos de Redes Sociais:

Genetic characterisation of adult primary pleomorphic uterine rhabdomyosarcoma and comparison with uterine carcinosarcoma

Ashley, Charles W ; Da Cruz Paula, Arnaud ; Ferrando, Lorenzo ; Gularte‐Mérida, Rodrigo ; Sebastiao, Ana P M ; Brown, David N ; Gazzo, Andrea M ; Pareja, Fresia ; Stylianou, Anthe ; Abu‐Rustum, Nadeem R ; Reis‐Filho, Jorge S ; Buehler, Darya ; Weisman, Paul ; Chiang, Sarah ; Weigelt, Britta

England: Wiley Subscription Services, Inc

Buscando em bases de dados remotas. Favor aguardar.