دورية أكاديمية
Collision of germline POLE and PMS2 variants in a young patient treated with immune checkpoint inhibitors
| العنوان: | Collision of germline POLE and PMS2 variants in a young patient treated with immune checkpoint inhibitors |
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| المؤلفون: | Enrico Berrino, Roberto Filippi, Clara Visintin, Serena Peirone, Elisabetta Fenocchio, Giovanni Farinea, Franco Veglio, Massimo Aglietta, Anna Sapino, Matteo Cereda, Rosella Visintin, Barbara Pasini, Caterina Marchi(`(o)) |
| المساهمون: | E. Berrino, R. Filippi, C. Visintin, S. Peirone, E. Fenocchio, G. Farinea, F. Veglio, M. Aglietta, A. Sapino, M. Cereda, R. Visintin, B. Pasini, C. Marchi(`(o)) |
| بيانات النشر: | Nature Research |
| سنة النشر: | 2022 |
| المجموعة: | The University of Milan: Archivio Istituzionale della Ricerca (AIR) |
| مصطلحات موضوعية: | Settore BIO/11 - Biologia Molecolare, Settore MED/03 - Genetica Medica |
| الوصف: | The onset of multiple and metachronous tumors in young patients induces to suspect the presence of genetic variants in genes associated with tumorigenesis. We describe here the unusual case of a 16-year-old patient who developed a synchronous bifocal colorectal adenocarcinoma with distant metastases. We provide high throughput molecular characterization with whole-exome sequencing (WES) and DNA targeted sequencing of different tumoral lesions and normal tissue samples that led to unveil a germline POLE mutation (p.Ser297Cys) coexisting with the PMS2 c.2174 + 1 G > A splicing mutation. This clinical scenario defines a "POLE-LYNCH" collision syndrome, which explains the ultra-mutator phenotype observed in the tumor lesions, and the presence of MMR deficiency-associated unusual signatures. The patient was successfully treated with immune checkpoint inhibitors but subsequently developed a high-grade urothelial carcinoma cured by surgery. We complement this analysis with a transcriptomic characterization of tumoral lesions with a panel targeting 770 genes related to the tumor microenvironment and immune evasion thus getting insight on cancer progression and response to immunotherapy. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/35260767; info:eu-repo/semantics/altIdentifier/wos/WOS:000766166400001; volume:6; issue:1; firstpage:1; lastpage:9; numberofpages:9; journal:NPJ PRECISION ONCOLOGY; http://hdl.handle.net/2434/915670Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85126245417 |
| DOI: | 10.1038/s41698-022-00258-8 |
| الإتاحة: | https://doi.org/10.1038/s41698-022-00258-8Test http://hdl.handle.net/2434/915670Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.73CFC743 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41698-022-00258-8 |
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