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Updated: Mar 8, 2026

Detection of Retrotransposition Activity of Hot LINE-1s by Long-Distance Inverse PCR
Published on: July 27, 2019
Insertions and Deletions Target Lineage-Defining Genes in Human Cancers
Marcin Imielinski1, Guangwu Guo2, Matthew Meyerson3
1Department of Pathology and Laboratory Medicine, Englander Institute for Precision Medicine, Institute for Computational Biomedicine, and Meyer Cancer Center, Weill Cornell Medicine, New York, NY 10065, USA; New York Genome Center, New York, NY 10013, USA.
Abstract:
Certain cell types function as factories, secreting large quantities of one or more proteins that are central to the physiology of the respective organ. Examples include surfactant proteins in lung alveoli, albumin in liver parenchyma, and lipase in the stomach lining. Whole-genome sequencing analysis of lung adenocarcinomas revealed noncoding somatic mutational hotspots near VMP1/MIR21 and indel hotspots in surfactant protein genes (SFTPA1, SFTPB, and SFTPC). Extrapolation to other solid cancers demonstrated highly recurrent and tumor-type-specific indel hotspots targeting the noncoding regions of highly expressed genes defining certain secretory cellular lineages: albumin (ALB) in liver carcinoma, gastric lipase (LIPF) in stomach carcinoma, and thyroglobulin (TG) in thyroid carcinoma. The sequence contexts of indels targeting lineage-defining genes were significantly enriched in the AATAATD DNA motif and specific chromatin contexts, including H3K27ac and H3K36me3. Our findings illuminate a prevalent and hitherto unrecognized mutational process linking cellular lineage and cancer.
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