EP 258: The mutations hiding in healthy tissues with Inigo Martincorena of the Wellcome Sanger Institute

This week on The Genetics Podcast, Patrick is joined by Dr. Inigo Martincorena, Group Leader at the Wellcome Sanger Institute. They discuss the discovery of widespread cancer-driver mutations in normal tissue, the role of somatic mutations in autoimmune disease, new sequencing technologies transforming the field, and the therapeutic potential of targeting these mutations.Show Notes0:00 Intro to The Genetics Podcast00:59 Welcome to Inigo 01:46 How Inigo's eyelid skin study revealed widespread cancer-driver mutations07:14 Findings from a follow-up study on esophageal tissue10:02 How NanoSeq technology scaled somatic mutation research across tissues12:34 The thyroid study linking somatic mutations to autoimmune disease17:07 How escaped B cell clones evolve into polyclonal autoimmune disease20:21 Immune gene mutations occurring in healthy aging lymphocytes21:21 Why driver mutation clones in normal tissue rarely become cancer24:16 Two therapeutic paradigms for targeting somatic mutations in disease28:13 Examples of somatic rescue mutations in the colon, liver, and blood29:20 Why clonal selection only occurs in dividing cell types31:20 The field's remaining blind spots in mobile immune cells and rare samples33:46 How new single-cell sequencing will link genotype to phenotype36:03 What Inigo has learned from collaborating across Sanger's expertise38:09 Closing remarksFind out moreEyelid studyEsophagus study