Detail
Článek
Článek online
FT
Medvik - BMČ
  • Je něco špatně v tomto záznamu ?

Search for Mutations Connected With Non-Response to Anti-EGFR Therapy in mCRC in the Morphologically Defined Regions of Primary Tumours

M. Čarnogurská, VS. Vasylieva, T. Macháčková, M. Boudná, L. Pifková, J. Orlíčková, TC. Ivkovic, O. Slabý, B. Bencsiková, V. Popovici, E. Budinská

. 2025 ; 14 (9) : e70910. [pub] -

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc25015842

Grantová podpora
825410 Horizon 2020 Framework Programme
19-03-00298 Ministerstvo Zdravotnictví Ceské Republiky

BACKGROUND: Emerging evidence suggests that tumour morphological heterogeneity may influence mutational profiles relevant to therapy response. In this pilot study, we aimed to assess whether mutations identified within specific morphological patterns or at the invasion front correlate with shorter time to progression after anti-EGFR therapy, as compared to whole-tissue analysis. METHODS: We investigated genetic mutations in 142 samples from primary tumours of 39 KRAS wild-type metastatic colorectal cancer (CRC) patients receiving anti-EGFR therapy. Deep next-generation sequencing was performed on whole-tumour sections and six morphology-defined tumour regions. RESULTS: Mutations in genes linked to anti-EGFR therapy response (KRAS, BRAF, NRAS, PTEN and PI3KCA) were found uniquely in the non-responder group, with substantial variability across morphological sub-regions. BRAF mutations were aligned with serrated and mucinous morphologies, while KRAS mutations (p.Lys147Glu and p.Ala146Thr) were associated with mucinous and desmoplastic morphologies. In all cases, the cumulative mutational profile from sub-regions provided more details than that of the whole-tumour profile. CONCLUSION: Our findings highlight that comprehensive analysis, considering morphological heterogeneity, is crucial for personalised CRC treatment strategies.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc25015842
003      
CZ-PrNML
005      
20250731091253.0
007      
ta
008      
250708s2025 xxu f 000 0|eng||
009      
AR
024    7_
$a 10.1002/cam4.70910 $2 doi
035    __
$a (PubMed)40302146
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxu
100    1_
$a Čarnogurská, Martina $u RECETOX, Faculty of Science, Masaryk University, Brno, Czech Republic $1 https://orcid.org/0009000637429224
245    10
$a Search for Mutations Connected With Non-Response to Anti-EGFR Therapy in mCRC in the Morphologically Defined Regions of Primary Tumours / $c M. Čarnogurská, VS. Vasylieva, T. Macháčková, M. Boudná, L. Pifková, J. Orlíčková, TC. Ivkovic, O. Slabý, B. Bencsiková, V. Popovici, E. Budinská
520    9_
$a BACKGROUND: Emerging evidence suggests that tumour morphological heterogeneity may influence mutational profiles relevant to therapy response. In this pilot study, we aimed to assess whether mutations identified within specific morphological patterns or at the invasion front correlate with shorter time to progression after anti-EGFR therapy, as compared to whole-tissue analysis. METHODS: We investigated genetic mutations in 142 samples from primary tumours of 39 KRAS wild-type metastatic colorectal cancer (CRC) patients receiving anti-EGFR therapy. Deep next-generation sequencing was performed on whole-tumour sections and six morphology-defined tumour regions. RESULTS: Mutations in genes linked to anti-EGFR therapy response (KRAS, BRAF, NRAS, PTEN and PI3KCA) were found uniquely in the non-responder group, with substantial variability across morphological sub-regions. BRAF mutations were aligned with serrated and mucinous morphologies, while KRAS mutations (p.Lys147Glu and p.Ala146Thr) were associated with mucinous and desmoplastic morphologies. In all cases, the cumulative mutational profile from sub-regions provided more details than that of the whole-tumour profile. CONCLUSION: Our findings highlight that comprehensive analysis, considering morphological heterogeneity, is crucial for personalised CRC treatment strategies.
650    _2
$a lidé $7 D006801
650    12
$a kolorektální nádory $x genetika $x farmakoterapie $x patologie $7 D015179
650    12
$a mutace $7 D009154
650    _2
$a ženské pohlaví $7 D005260
650    _2
$a mužské pohlaví $7 D008297
650    _2
$a erbB receptory $x antagonisté a inhibitory $7 D066246
650    _2
$a lidé středního věku $7 D008875
650    _2
$a senioři $7 D000368
650    _2
$a protoonkogenní proteiny B-Raf $x genetika $7 D048493
650    _2
$a vysoce účinné nukleotidové sekvenování $7 D059014
650    _2
$a protoonkogenní proteiny p21(ras) $x genetika $7 D016283
650    _2
$a pilotní projekty $7 D010865
650    12
$a chemorezistence $x genetika $7 D019008
650    _2
$a senioři nad 80 let $7 D000369
650    12
$a inhibitory proteinkinas $x terapeutické užití $7 D047428
650    _2
$a dospělí $7 D000328
650    _2
$a fosfohydroláza PTEN $x genetika $7 D051059
650    _2
$a mutační analýza DNA $7 D004252
650    12
$a protinádorové látky $x terapeutické užití $7 D000970
650    _2
$a GTP-fosfohydrolasy $x genetika $7 D020558
655    _2
$a časopisecké články $7 D016428
700    1_
$a Vasylieva, Valeriia Serhiivna $u RECETOX, Faculty of Science, Masaryk University, Brno, Czech Republic
700    1_
$a Macháčková, Táňa $u Central European Institute of Technology, Masaryk University, Brno, Czech Republic $u Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic
700    1_
$a Boudná, Marie $u Central European Institute of Technology, Masaryk University, Brno, Czech Republic $u Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic
700    1_
$a Pifková, Lucie $u Central European Institute of Technology, Masaryk University, Brno, Czech Republic $u Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic
700    1_
$a Orlíčková, Jana $u Central European Institute of Technology, Masaryk University, Brno, Czech Republic $u Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic
700    1_
$a Ivkovic, Tina Catela $u Central European Institute of Technology, Masaryk University, Brno, Czech Republic
700    1_
$a Slabý, Ondrej $u Central European Institute of Technology, Masaryk University, Brno, Czech Republic $u Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic $1 https://orcid.org/0000000284500584 $7 js20030220015
700    1_
$a Bencsiková, Beatrix $u Masaryk Memorial Cancer Institute, Brno, Czech Republic
700    1_
$a Popovici, Vlad $u RECETOX, Faculty of Science, Masaryk University, Brno, Czech Republic
700    1_
$a Budinská, Eva $u RECETOX, Faculty of Science, Masaryk University, Brno, Czech Republic
773    0_
$w MED00181704 $t Cancer medicine $x 2045-7634 $g Roč. 14, č. 9 (2025), s. e70910
856    41
$u https://pubmed.ncbi.nlm.nih.gov/40302146 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y - $z 0
990    __
$a 20250708 $b ABA008
991    __
$a 20250731091247 $b ABA008
999    __
$a ok $b bmc $g 2366578 $s 1252967
BAS    __
$a 3
BAS    __
$a PreBMC-MEDLINE
BMC    __
$a 2025 $b 14 $c 9 $d e70910 $e - $i 2045-7634 $m Cancer medicine $n Cancer Med $x MED00181704
GRA    __
$a 825410 $p Horizon 2020 Framework Programme
GRA    __
$a 19-03-00298 $p Ministerstvo Zdravotnictví Ceské Republiky
LZP    __
$a Pubmed-20250708

Najít záznam

Citační ukazatele

Možnosti archivace