• Je něco špatně v tomto záznamu ?

Molecular Profiling of Sinonasal Adenoid Cystic Carcinoma: Canonical and Noncanonical Gene Fusions and Mutation

A. Skálová, M. Bradová, A. Agaimy, J. Laco, C. Badual, S. Ihrler, I. Damjanov, NJ. Rupp, CE. Bacchi, S. Mueller, S. Ventelä, D. Zhang, E. Comperat, P. Martínek, R. Šíma, T. Vaněček, P. Grossmann, P. Steiner, V. Hájková, I. Kovářová, M. Michal, I. Leivo

. 2025 ; 49 (3) : 227-242. [pub] 20250106

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc25009706

Adenoid cystic carcinomas (AdCC) of salivary gland origin have long been categorized as fusion-defined carcinomas owing to the almost universal presence of the gene fusion MYB::NFIB , or less commonly MYBL1::NFIB. Sinonasal AdCC is an aggressive salivary gland malignancy with no effective systemic therapy. Therefore, it is urgent to search for potentially targetable genetic alterations associated with AdCC. We have searched the authors' registries and selected all AdCCs arising in the sinonasal tract. The tumors were examined histologically, immunohistochemically, by next generation sequencing (NGS) and/or fluorescence in situ hybridization (FISH) looking for MYB/MYBL1 and/or NFIB gene fusions or any novel gene fusions and/or mutations. In addition, all tumors were tested for HPV by genotyping using (q)PCR. Our cohort comprised 88 cases of sinonasal AdCC, predominantly characterized by canonical MYB::NFIB (49 cases) and MYBL1::NFIB (9 cases) fusions. In addition, noncanonical fusions EWSR1::MYB ; ACTB::MYB; ESRRG::DNM3 , and ACTN4::MYB were identified by NGS, each of them in 1 case. Among nine fusion-negative AdCCs, FISH detected rearrangements in MYB (7 cases) , NFIB (1 case), and EWSR1 (1 case). Six AdCCs lacked fusions or gene rearrangements, while 11 cases were unanalyzable. Mutational analysis was performed by NGS in 31/88 (35%) AdCCs. Mutations in genes with established roles in oncogenesis were identified in 21/31 tumors (68%), including BCOR (4/21; 19%), NOTCH1 (3/21; 14%), EP300 (3/21; 14%), SMARCA4 (2/21; 9%), RUNX1 (2/21; 9%), KDM6A (2/21; 9%), SPEN (2/21; 9%), and RIT1, MGA, RB1, PHF6, PTEN, CREBBP, DDX41, CHD2, ROS1, TAF1, CCD1, NF1, PALB2, AVCR1B, ARID1A, PPM1D, LZTR1, GEN1 , PDGFRA , each in 1 case (1/21; 5%). Additional 24 cases exhibited a spectrum of gene mutations of uncertain pathogenetic significance. No morphologic differences were observed between AdCCs with MYBL1::NFIB and MYB::NFIB fusions. Interestingly, mutations in the NOTCH genes were seen in connection with both canonical and noncanonical fusions, and often associated with high-grade histology or metatypical phenotype, as well as with poorer clinical outcome. Noncanonical fusions were predominantly observed in metatypical AdCCs. These findings emphasize the value of comprehensive molecular profiling in correlating morphologic characteristics, genetic landscape, and clinical behavior in AdCC.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc25009706
003      
CZ-PrNML
005      
20250429134501.0
007      
ta
008      
250415s2025 xxu f 000 0|eng||
009      
AR
024    7_
$a 10.1097/PAS.0000000000002349 $2 doi
035    __
$a (PubMed)39760648
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxu
100    1_
$a Skálová, Alena $u Department of Pathology, Charles University, Faculty of Medicine in Pilsen $u Bioptic Laboratory Ltd
245    10
$a Molecular Profiling of Sinonasal Adenoid Cystic Carcinoma: Canonical and Noncanonical Gene Fusions and Mutation / $c A. Skálová, M. Bradová, A. Agaimy, J. Laco, C. Badual, S. Ihrler, I. Damjanov, NJ. Rupp, CE. Bacchi, S. Mueller, S. Ventelä, D. Zhang, E. Comperat, P. Martínek, R. Šíma, T. Vaněček, P. Grossmann, P. Steiner, V. Hájková, I. Kovářová, M. Michal, I. Leivo
520    9_
$a Adenoid cystic carcinomas (AdCC) of salivary gland origin have long been categorized as fusion-defined carcinomas owing to the almost universal presence of the gene fusion MYB::NFIB , or less commonly MYBL1::NFIB. Sinonasal AdCC is an aggressive salivary gland malignancy with no effective systemic therapy. Therefore, it is urgent to search for potentially targetable genetic alterations associated with AdCC. We have searched the authors' registries and selected all AdCCs arising in the sinonasal tract. The tumors were examined histologically, immunohistochemically, by next generation sequencing (NGS) and/or fluorescence in situ hybridization (FISH) looking for MYB/MYBL1 and/or NFIB gene fusions or any novel gene fusions and/or mutations. In addition, all tumors were tested for HPV by genotyping using (q)PCR. Our cohort comprised 88 cases of sinonasal AdCC, predominantly characterized by canonical MYB::NFIB (49 cases) and MYBL1::NFIB (9 cases) fusions. In addition, noncanonical fusions EWSR1::MYB ; ACTB::MYB; ESRRG::DNM3 , and ACTN4::MYB were identified by NGS, each of them in 1 case. Among nine fusion-negative AdCCs, FISH detected rearrangements in MYB (7 cases) , NFIB (1 case), and EWSR1 (1 case). Six AdCCs lacked fusions or gene rearrangements, while 11 cases were unanalyzable. Mutational analysis was performed by NGS in 31/88 (35%) AdCCs. Mutations in genes with established roles in oncogenesis were identified in 21/31 tumors (68%), including BCOR (4/21; 19%), NOTCH1 (3/21; 14%), EP300 (3/21; 14%), SMARCA4 (2/21; 9%), RUNX1 (2/21; 9%), KDM6A (2/21; 9%), SPEN (2/21; 9%), and RIT1, MGA, RB1, PHF6, PTEN, CREBBP, DDX41, CHD2, ROS1, TAF1, CCD1, NF1, PALB2, AVCR1B, ARID1A, PPM1D, LZTR1, GEN1 , PDGFRA , each in 1 case (1/21; 5%). Additional 24 cases exhibited a spectrum of gene mutations of uncertain pathogenetic significance. No morphologic differences were observed between AdCCs with MYBL1::NFIB and MYB::NFIB fusions. Interestingly, mutations in the NOTCH genes were seen in connection with both canonical and noncanonical fusions, and often associated with high-grade histology or metatypical phenotype, as well as with poorer clinical outcome. Noncanonical fusions were predominantly observed in metatypical AdCCs. These findings emphasize the value of comprehensive molecular profiling in correlating morphologic characteristics, genetic landscape, and clinical behavior in AdCC.
650    _2
$a lidé $7 D006801
650    12
$a adenoidně cystický karcinom $x genetika $x patologie $7 D003528
650    _2
$a lidé středního věku $7 D008875
650    _2
$a mužské pohlaví $7 D008297
650    _2
$a ženské pohlaví $7 D005260
650    _2
$a senioři $7 D000368
650    12
$a mutace $7 D009154
650    _2
$a dospělí $7 D000328
650    12
$a nádory vedlejších dutin nosních $x genetika $x patologie $7 D010255
650    12
$a nádorové biomarkery $x genetika $7 D014408
650    12
$a hybridizace in situ fluorescenční $7 D017404
650    12
$a vysoce účinné nukleotidové sekvenování $7 D059014
650    _2
$a senioři nad 80 let $7 D000369
650    _2
$a mladý dospělý $7 D055815
650    _2
$a fúzní onkogenní proteiny $x genetika $7 D015514
650    _2
$a imunohistochemie $7 D007150
650    _2
$a mutační analýza DNA $7 D004252
650    _2
$a fúze genů $7 D050939
650    _2
$a fenotyp $7 D010641
650    _2
$a genetická predispozice k nemoci $7 D020022
650    _2
$a transkripční faktory NFI $x genetika $7 D051839
650    _2
$a mladiství $7 D000293
655    _2
$a časopisecké články $7 D016428
700    1_
$a Bradová, Martina $u Department of Pathology, Charles University, Faculty of Medicine in Pilsen $u Bioptic Laboratory Ltd
700    1_
$a Agaimy, Abbas $u Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg (FAU)
700    1_
$a Laco, Jan $u The Fingerland Department of Pathology, Charles University, Faculty of Medicine and University Hospital Hradec Kralove, Hradec Kralove, Czech Republic
700    1_
$a Badual, Cécile $u Service d'Anatomo-Pathologie, Department of Pathology, Hôpital Européen G Pompidou, APHP, Université de Paris
700    1_
$a Ihrler, Stephan $u Dermpath, Muenchen, Germany
700    1_
$a Damjanov, Ivan $u The University of Kansas School of Medicine
700    1_
$a Rupp, Niels J $u Department of Pathology, and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland
700    1_
$a Bacchi, Carlos E $u Consultoria em Patologia, Botucatu, São Paulo, Brazil
700    1_
$a Mueller, Sarina $u Department of Otorhinolaryngology and Head and Neck Surgery, University Hospital Erlangen, Erlanden
700    1_
$a Ventelä, Sami $u Departments of Otorhinolaryngology
700    1_
$a Zhang, Da $u Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, Kansas City, KS
700    1_
$a Comperat, Eva $u Department of Pathology, Tenon Hospital, Sorbonne University, Paris, France $u Department of Pathology, Medical University of Vienna, Vienna, Austria
700    1_
$a Martínek, Petr $u Molecular and Genetic Laboratory, Bioptic Laboratory Ltd, Pilsen
700    1_
$a Šíma, Radek $u Department of Pathology, Charles University, Faculty of Medicine in Pilsen $u Molecular and Genetic Laboratory, Bioptic Laboratory Ltd, Pilsen
700    1_
$a Vaněček, Tomas $u Molecular and Genetic Laboratory, Bioptic Laboratory Ltd, Pilsen
700    1_
$a Grossmann, Petr $u Molecular and Genetic Laboratory, Bioptic Laboratory Ltd, Pilsen
700    1_
$a Steiner, Petr $u Molecular and Genetic Laboratory, Bioptic Laboratory Ltd, Pilsen
700    1_
$a Hájková, Veronka $u Molecular and Genetic Laboratory, Bioptic Laboratory Ltd, Pilsen
700    1_
$a Kovářová, Inka $u Department of Pathology, Charles University, Faculty of Medicine in Pilsen
700    1_
$a Michal, Michal $u Department of Pathology, Charles University, Faculty of Medicine in Pilsen $u Bioptic Laboratory Ltd
700    1_
$a Leivo, Ilmo $u Pathology, Turku University Hospital $u Institute of Biomedicine, Pathology, University of Turku, Turku, Finland
773    0_
$w MED00000304 $t The American journal of surgical pathology $x 1532-0979 $g Roč. 49, č. 3 (2025), s. 227-242
856    41
$u https://pubmed.ncbi.nlm.nih.gov/39760648 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y - $z 0
990    __
$a 20250415 $b ABA008
991    __
$a 20250429134456 $b ABA008
999    __
$a ok $b bmc $g 2311215 $s 1246787
BAS    __
$a 3
BAS    __
$a PreBMC-MEDLINE
BMC    __
$a 2025 $b 49 $c 3 $d 227-242 $e 20250106 $i 1532-0979 $m The American journal of surgical pathology $n Am J Surg Pathol $x MED00000304
LZP    __
$a Pubmed-20250415

Najít záznam

Citační ukazatele

Možnosti archivace