Details

Autor(en) / Beteiligte

• Giner-Calabuig, Mar
• De Leon, Seila
• Wang, Julian
• Fehlmann, Tara D
• Ukaegbu, Chinedu
• Gibson, Joanna
• Alustiza-Fernandez, Miren
• Pico, Maria-Dolores
• Alenda, Cristina
• Herraiz, Maite
• Carrillo-Palau, Marta
• Salces, Inmaculada
• Reyes, Josep
• Ortega, Silvia P
• Obrador-Hevia, Antònia
• Cecchini, Michael
• Syngal, Sapna
• Stoffel, Elena
• Ellis, Nathan A
• Sweasy, Joann
• Jover, Rodrigo
• Llor, Xavier
• Xicola, Rosa M

Titel

Mutational signature profiling classifies subtypes of clinically different mismatch-repair-deficient tumours with a differential immunogenic response potential

Ist Teil von

• British journal of cancer, 2022-06, Vol.126 (11), p.1595-1603

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2022

Quelle

MEDLINE

Beschreibungen/Notizen

• Mismatch repair (MMR) deficiency is the hallmark of tumours from Lynch syndrome (LS), sporadic MLH1 hypermethylated and Lynch-like syndrome (LLS), but there is a lack of understanding of the variability in their mutational profiles based on clinical phenotypes. The aim of this study was to perform a molecular characterisation to identify novel features that can impact tumour behaviour and clinical management. We tested 105 MMR-deficient colorectal cancer tumours (25 LS, 35 LLS and 45 sporadic) for global exome microsatellite instability, cancer mutational signatures, mutational spectrum and neoepitope load. Fifty-three percent of tumours showed high contribution of MMR-deficient mutational signatures, high level of global exome microsatellite instability, loss of MLH1/PMS2 protein expression and included sporadic tumours. Thirty-one percent of tumours showed weaker features of MMR deficiency, 62% lost MSH2/MSH6 expression and included 60% of LS and 44% of LLS tumours. Remarkably, 9% of all tumours lacked global exome microsatellite instability. Lastly, HLA-B07:02 could be triggering the neoantigen presentation in tumours that show the strongest contribution of MMR-deficient tumours. Next-generation sequencing approaches allow for a granular molecular characterisation of MMR-deficient tumours, which can be essential to properly diagnose and treat patients with these tumours in the setting of personalised medicine.