Fig. 6: Further evidence of Whole Intron deletions in cells and tumors.

a Example of consecutive WIDs detected in the GNAS gene from patient samples sequenced with MSK-IMPACT. Grey bases match the reference genome, and deletions are indicated with a black dash (–). On the left, three deletions were observed at the GNAS gene following targeted NGS, precisely mapping the introns flanked by Exon 10–11, 11–12, and 12–13, respectively. On the right, five consecutive deletions were mapped to introns flanked by Exon 8–9, 9–10, 10–11, 11–12, and 12–13. b Frequency of consecutive WIDs observed in the MSK-IMPACT dataset. c Loss of upstream intron following cleavage of CALR intron 2 with CRISPR/Cas9. Top, schematic representation of multiple introns in CALR gene with cleavage of intron 2. The bottom graph depicts the quantification of reads containing WIDs in an intron adjacent to the cleavage site (n = 3 biological replicates). Statistical significance was assessed using an unpaired two-tailed t-tests. Error bars represent the standard error of the mean (± SEM). d Proposed model for RT-DSBR: When a double-strand break (DSB) occurs within an actively transcribed gene, the existing RNA transcript base-pairs with the cleaved template strand and is reverse transcribed by the Polζ complex. The newly synthesized DNA (shown in red) anneals to the resected opposite end, facilitating second-strand synthesis, gap filling, and ligation. The specific polymerase and ligase involved in this process have yet to be identified. If a spliced RNA transcript serves as the repair template, the intronic sequence will be omitted, resulting in a genetic scar known as a whole intron deletion (WID). Schematic in this figure (d) was created in BioRender. (2025) https://BioRender.com/9tmc1xb. Source data are provided as a Source Data file.