Redefined indel taxonomy reveals insights into mutational signatures
Publication: Nature Genetics
Gene Ching Chiek Koh, Arjun Scott Nanda, Giuseppe Rinaldi, Soraya Boushaki, Andrea Degasperi, Cherif Badja, Andrew Marcel Pregnall, Salome Jingchen Zhao, Lucia Chmelova, Daniella Black, Laura Heskin, João Dias, Jamie Young, Yasin Memari, Scott Shooter, Jan Czarnecki, Matthew Arthur Brown, Helen Ruth Davies, Xueqing Zou & Serena Nik-Zainal
10 April 2025
In cancer genetics, small insertions and deletions (called InDels) have not been as widely researched as substitutions (both causes of cancer). Researchers created identical ‘CRISPR-edited’ human cell models of ones which were damaged and then replicated (damaged included mismatched repairs and replicative enzymes). The trail that led to these mutations were uncovered and current research was unable to show the cancerous mutations apart from more general mutations.
To address this, a technique called InDel was developed that was able to pick up unusual genetic sequences and very long long genetic sequences that meant they could be classified into 89 subtypes. By using the information collected in the 100K Genomes Project, 37 InDel sequences were found, 27 of these were new. In addition to this new finding, a new mechanism called PRRDetect was developed which allowed tumours to be ‘classified’ possibly having implications for immunotherapy, a way of treating cancerous tumours.
