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 Notes
0:00 Intro to The Genetics Podcast
00:59 Welcome to Inigo
01:46 How Inigo's eyelid skin study revealed widespread cancer-driver mutations
07:14 Findings from a follow-up study on esophageal tissue
10:02 How NanoSeq technology scaled somatic mutation research across tissues
12:34 The thyroid study linking somatic mutations to autoimmune disease
17:07 How escaped B cell clones evolve into polyclonal autoimmune disease
20:21 Immune gene mutations occurring in healthy aging lymphocytes
21:21 Why driver mutation clones in normal tissue rarely become cancer
24:16 Two therapeutic paradigms for targeting somatic mutations in disease
28:13 Examples of somatic rescue mutations in the colon, liver, and blood
29:20 Why clonal selection only occurs in dividing cell types
31:20 The field's remaining blind spots in mobile immune cells and rare samples
33:46 How new single-cell sequencing will link genotype to phenotype
36:03 What Inigo has learned from collaborating across Sanger's expertise
38:09 Closing remarks
Find out more
