-
Je něco špatně v tomto záznamu ?
Molecular substratification of endometrial carcinomas with no special molecular profile (NSMP) by using a limited NGS custom panel may facilitate effective patient selection for the PIK3CA-targeted therapy
O. Ondič, K. Michalová, M. Švajdler, J. Presl, J. Kosťun, V. Hájková, P. Martínek, M. Michal
Jazyk angličtina
Typ dokumentu časopisecké články
- MeSH
- cílená molekulární terapie MeSH
- dospělí MeSH
- fosfatidylinositol-3-kinasy třídy I * genetika antagonisté a inhibitory MeSH
- lidé středního věku MeSH
- lidé MeSH
- mutace MeSH
- mutační analýza DNA MeSH
- nádorové biomarkery * genetika MeSH
- nádory endometria * genetika patologie farmakoterapie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- výběr pacientů MeSH
- vysoce účinné nukleotidové sekvenování * metody MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Endometrial carcinomas (EC) of no special molecular profile (NSMP) represent the largest molecular category of EC, comprising a mixture of tumors with different histology and molecular profiles. These facts likely point to different tumor biology, clinical outcomes, and targeted therapy responses within this molecular category. The PIK3CA is currently the only targetable kinase oncoprotein directly implicated in EC carcinogenesis. Investigating a unique single-institution cohort, we attempted to stratify NSMP ECs based on the presence of the PIK3CA pathogenic mutation. Those cases were further analyzed for other well-established-associated oncogenic driver gene mutations. Histological and clinical variables were also correlated in each case. Altogether, 175 ECs were prospectively tested by a limited custom NGS panel containing ARID1A, BCOR, BRCA1, BRCA2, CTNNB1, KRAS, MLH1, MSH2, MSH6, NRAS, PIK3CA, PMS2, POLD1, POLE, PTEN,and TP53 genes. We identified 24 PIK3CA mutated cases in the group of 80 NSMP ECs, with another co-occurring mutation in at least one oncogenic driver gene (CTNNB1, PTEN, ARID1A, KRAS, BCOR, PMS2) in 19 cases. In conclusion, a limited NGS panel can effectively test EC tissue for specific pathogenetically relevant oncogene mutations. The NSMP EC category contains 30% of the PIK3CA mutated cases. Of those, 21% contain the PIK3CA mutation as a sole EC-associated oncogene mutation, while 79% harbor at least one more mutated gene. These findings may inform future healthcare planning and improve the effectiveness of EC patient selection for the PIK3CA-targeted therapy.
Department of Pathology Medical Faculty in Pilsen Charles University Prague Czech Republic
Molecular Genetics Department Bioptická Laboratoř s r o Pilsen Czech Republic
Citace poskytuje Crossref.org
- 000
- 00000naa a2200000 a 4500
- 001
- bmc25016319
- 003
- CZ-PrNML
- 005
- 20250731092826.0
- 007
- ta
- 008
- 250708s2025 gw f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1007/s00428-024-03905-6 $2 doi
- 035 __
- $a (PubMed)39235514
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a x
- 100 1_
- $a Ondič, Ondrej $u Department of Pathology, Medical Faculty in Pilsen, Charles University, Prague, Czech Republic. ondic@biopticka.cz $u Molecular Genetics Department, Bioptická Laboratoř s.r.o, Pilsen, Czech Republic. ondic@biopticka.cz $1 https://orcid.org/0000000240385641 $7 xx0106803
- 245 10
- $a Molecular substratification of endometrial carcinomas with no special molecular profile (NSMP) by using a limited NGS custom panel may facilitate effective patient selection for the PIK3CA-targeted therapy / $c O. Ondič, K. Michalová, M. Švajdler, J. Presl, J. Kosťun, V. Hájková, P. Martínek, M. Michal
- 520 9_
- $a Endometrial carcinomas (EC) of no special molecular profile (NSMP) represent the largest molecular category of EC, comprising a mixture of tumors with different histology and molecular profiles. These facts likely point to different tumor biology, clinical outcomes, and targeted therapy responses within this molecular category. The PIK3CA is currently the only targetable kinase oncoprotein directly implicated in EC carcinogenesis. Investigating a unique single-institution cohort, we attempted to stratify NSMP ECs based on the presence of the PIK3CA pathogenic mutation. Those cases were further analyzed for other well-established-associated oncogenic driver gene mutations. Histological and clinical variables were also correlated in each case. Altogether, 175 ECs were prospectively tested by a limited custom NGS panel containing ARID1A, BCOR, BRCA1, BRCA2, CTNNB1, KRAS, MLH1, MSH2, MSH6, NRAS, PIK3CA, PMS2, POLD1, POLE, PTEN,and TP53 genes. We identified 24 PIK3CA mutated cases in the group of 80 NSMP ECs, with another co-occurring mutation in at least one oncogenic driver gene (CTNNB1, PTEN, ARID1A, KRAS, BCOR, PMS2) in 19 cases. In conclusion, a limited NGS panel can effectively test EC tissue for specific pathogenetically relevant oncogene mutations. The NSMP EC category contains 30% of the PIK3CA mutated cases. Of those, 21% contain the PIK3CA mutation as a sole EC-associated oncogene mutation, while 79% harbor at least one more mutated gene. These findings may inform future healthcare planning and improve the effectiveness of EC patient selection for the PIK3CA-targeted therapy.
- 650 _2
- $a lidé $7 D006801
- 650 _2
- $a ženské pohlaví $7 D005260
- 650 12
- $a fosfatidylinositol-3-kinasy třídy I $x genetika $x antagonisté a inhibitory $7 D058534
- 650 12
- $a nádory endometria $x genetika $x patologie $x farmakoterapie $7 D016889
- 650 12
- $a vysoce účinné nukleotidové sekvenování $x metody $7 D059014
- 650 _2
- $a lidé středního věku $7 D008875
- 650 _2
- $a mutace $7 D009154
- 650 _2
- $a senioři $7 D000368
- 650 _2
- $a výběr pacientů $7 D018579
- 650 12
- $a nádorové biomarkery $x genetika $7 D014408
- 650 _2
- $a cílená molekulární terapie $7 D058990
- 650 _2
- $a dospělí $7 D000328
- 650 _2
- $a senioři nad 80 let $7 D000369
- 650 _2
- $a mutační analýza DNA $7 D004252
- 655 _2
- $a časopisecké články $7 D016428
- 700 1_
- $a Michalová, Květoslava $u Department of Pathology, Medical Faculty in Pilsen, Charles University, Prague, Czech Republic $u Molecular Genetics Department, Bioptická Laboratoř s.r.o, Pilsen, Czech Republic
- 700 1_
- $a Švajdler, Marián $u Department of Pathology, Medical Faculty in Pilsen, Charles University, Prague, Czech Republic $u Molecular Genetics Department, Bioptická Laboratoř s.r.o, Pilsen, Czech Republic
- 700 1_
- $a Presl, Jiří $u Department of Gynecology and Obstetrics, Medical Faculty in Pilsen, Charles University, Prague, Czech Republic
- 700 1_
- $a Kosťun, Jan $u Department of Gynecology and Obstetrics, Medical Faculty in Pilsen, Charles University, Prague, Czech Republic
- 700 1_
- $a Hájková, Veronika $u Molecular Genetics Department, Bioptická Laboratoř s.r.o, Pilsen, Czech Republic
- 700 1_
- $a Martínek, Petr $u Molecular Genetics Department, Bioptická Laboratoř s.r.o, Pilsen, Czech Republic
- 700 1_
- $a Michal, Michal $u Department of Pathology, Medical Faculty in Pilsen, Charles University, Prague, Czech Republic
- 773 0_
- $w MED00004660 $t Virchows Archiv $x 1432-2307 $g Roč. 486, č. 4 (2025), s. 827-832
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/39235514 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y - $z 0
- 990 __
- $a 20250708 $b ABA008
- 991 __
- $a 20250731092821 $b ABA008
- 999 __
- $a ok $b bmc $g 2366879 $s 1253444
- BAS __
- $a 3
- BAS __
- $a PreBMC-MEDLINE
- BMC __
- $a 2025 $b 486 $c 4 $d 827-832 $e 20240905 $i 1432-2307 $m Virchows Archiv $n Virchows Arch $x MED00004660
- LZP __
- $a Pubmed-20250708
