Inigo Martincorena | Group Leader

Martincorena, Inigo

Inigo is a group leader at the Sanger Institute investigating somatic mutation in cancer and normal cells.

With a background in molecular biology, bioinformatics and evolutionary genomics, my research focuses on understanding cancer progression as a result of somatic mutation and selection.

Over the past few years, systematic sequencing of tumours has revolutionised our understanding of the genetics of cancer. This has revealed that most cancers carry thousands of mutations in their genomes, accumulated through the lifetime of their cells. However, owing to technical limitations, very little is known about the earliest steps of cancer and how normal cells in our tissues accumulate mutations during ageing and in their progression towards cancer. We investigate these early changes by studying somatic evolution in normal and precancerous tissues.

In 2015 we published the first comprehensive description of somatic mutation and selection in a healthy solid tissue, revealing that human skin is a patchwork of thousands of competing clones carrying cancer-driver mutations (Martincorena et al., 2015). At that time, it was unclear whether sun-exposed skin was an exceptional tissue, owing to a lifetime of sun damage. To our surprise, we later discovered that the same phenomenon takes place at even greater scale in normal oesophagus, with over half of all epithelial cells carrying canonical cancer-driving mutations by middle age as a result of hundreds of microscopic clonal expansions per square centimetre (Martincorena et al., 2018).

These findings revealed how little we know about how our cells mutate and compete during life and raised questions about their role in cancer and ageing. Our current research focuses on understanding the extent of somatic evolution in normal tissues, including studies on early cancer development, studies exploring the impact of somatic mutation in diseases unrelated to cancer and forays into somatic mutation in other species.

I also work on adapting evolutionary methods to cancer genomics and on the development of computational methods for discovering new cancer genes and non-coding driver mutations. This includes the development of dNdScv, an evolutionary method to study selection in cancer and identify driver genes from cancer genomics data.

Publications

  • Somatic mutant clones colonize the human esophagus with age.

    Martincorena I, Fowler JC, Wabik A, Lawson ARJ, Abascal F et al.

    Science (New York, N.Y.) 2018;362;6417;911-917

  • Universal Patterns of Selection in Cancer and Somatic Tissues.

    Martincorena I, Raine KM, Gerstung M, Dawson KJ, Haase K et al.

    Cell 2017;171;5;1029-1041.e21

  • Tumor evolution. High burden and pervasive positive selection of somatic mutations in normal human skin.

    Martincorena I, Roshan A, Gerstung M, Ellis P, Van Loo P et al.

    Science (New York, N.Y.) 2015;348;6237;880-6

  • Somatic mutation in cancer and normal cells.

    Martincorena I and Campbell PJ

    Science (New York, N.Y.) 2015;349;6255;1483-9

  • Somatic mutations reveal asymmetric cellular dynamics in the early human embryo.

    Ju YS, Martincorena I, Gerstung M, Petljak M, Alexandrov LB et al.

    Nature 2017;543;7647;714-718

  • Precision oncology for acute myeloid leukemia using a knowledge bank approach.

    Gerstung M, Papaemmanuil E, Martincorena I, Bullinger L, Gaidzik VI et al.

    Nature genetics 2017;49;3;332-340

  • Population dynamics of normal human blood inferred from somatic mutations.

    Lee-Six H, Øbro NF, Shepherd MS, Grossmann S, Dawson K et al.

    Nature 2018;561;7724;473-478

  • Mutational signatures associated with tobacco smoking in human cancer.

    Alexandrov LB, Ju YS, Haase K, Van Loo P, Martincorena I et al.

    Science (New York, N.Y.) 2016;354;6312;618-622

  • Tissue-specific mutation accumulation in human adult stem cells during life.

    Blokzijl F, de Ligt J, Jager M, Sasselli V, Roerink S et al.

    Nature 2016;538;7624;260-264

  • Mutational signatures associated with tobacco smoking in human cancer.

    Alexandrov LB, Ju YS, Haase K, Van Loo P, Martincorena I et al.

    Science (New York, N.Y.) 2016;354;6312;618-622

  • Landscape of somatic mutations in 560 breast cancer whole-genome sequences.

    Nik-Zainal S, Davies H, Staaf J, Ramakrishna M, Glodzik D et al.

    Nature 2016;534;7605;47-54

  • Evidence of non-random mutation rates suggests an evolutionary risk management strategy.

    Martincorena I, Seshasayee AS and Luscombe NM

    Nature 2012;485;7396;95-8

  • Genomic Classification and Prognosis in Acute Myeloid Leukemia.

    Papaemmanuil E, Gerstung M, Bullinger L, Gaidzik VI, Paschka P et al.

    The New England journal of medicine 2016;374;23;2209-2221

  • Genome sequencing of normal cells reveals developmental lineages and mutational processes.

    Behjati S, Huch M, van Boxtel R, Karthaus W, Wedge DC et al.

    Nature 2014;513;7518;422-425

  • Mobile DNA in cancer. Extensive transduction of nonrepetitive DNA mediated by L1 retrotransposition in cancer genomes.

    Tubio JMC, Li Y, Ju YS, Martincorena I, Cooke SL et al.

    Science (New York, N.Y.) 2014;345;6196;1251343

  • Transmissible [corrected] dog cancer genome reveals the origin and history of an ancient cell lineage.

    Murchison EP, Wedge DC, Alexandrov LB, Fu B, Martincorena I et al.

    Science (New York, N.Y.) 2014;343;6169;437-440

  • Inactivating CUX1 mutations promote tumorigenesis.

    Wong CC, Martincorena I, Rust AG, Rashid M, Alifrangis C et al.

    Nature genetics 2014;46;1;33-8

  • RAG-mediated recombination is the predominant driver of oncogenic rearrangement in ETV6-RUNX1 acute lymphoblastic leukemia.

    Papaemmanuil E, Rapado I, Li Y, Potter NE, Wedge DC et al.

    Nature genetics 2014;46;2;116-25

  • Recurrent PTPRB and PLCG1 mutations in angiosarcoma.

    Behjati S, Tarpey PS, Sheldon H, Martincorena I, Van Loo P et al.

    Nature genetics 2014;46;4;376-379

  • Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2.

    Nangalia J, Massie CE, Baxter EJ, Nice FL, Gundem G et al.

    The New England journal of medicine 2013;369;25;2391-2405

  • Direct competition between hnRNP C and U2AF65 protects the transcriptome from the exonization of Alu elements.

    Zarnack K, König J, Tajnik M, Martincorena I, Eustermann S et al.

    Cell 2013;152;3;453-66

  • Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing.

    Cortés-Ciriano I, Lee JJ, Xi R, Jain D, Jung YL et al.

    Nature genetics 2020;52;3;331-341

  • Comprehensive molecular characterization of mitochondrial genomes in human cancers.

    Yuan Y, Ju YS, Kim Y, Li J, Wang Y et al.

    Nature genetics 2020;52;3;342-352

  • Disruption of chromatin folding domains by somatic genomic rearrangements in human cancer.

    Akdemir KC, Le VT, Chandran S, Li Y, Verhaak RG et al.

    Nature genetics 2020;52;3;294-305

  • Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotransposition.

    Rodriguez-Martin B, Alvarez EG, Baez-Ortega A, Zamora J, Supek F et al.

    Nature genetics 2020;52;3;306-319

  • Long-term expansion, genomic stability and in vivo safety of adult human pancreas organoids.

    Georgakopoulos N, Prior N, Angres B, Mastrogiovanni G, Cagan A et al.

    BMC developmental biology 2020;20;1;4

  • Cancer LncRNA Census reveals evidence for deep functional conservation of long noncoding RNAs in tumorigenesis.

    Carlevaro-Fita J, Lanzós A, Feuerbach L, Hong C, Mas-Ponte D et al.

    Communications biology 2020;3;1;56

  • Combined burden and functional impact tests for cancer driver discovery using DriverPower.

    Shuai S, PCAWG Drivers and Functional Interpretation Working Group, Gallinger S, Stein L and PCAWG Consortium

    Nature communications 2020;11;1;734

  • Genomic footprints of activated telomere maintenance mechanisms in cancer.

    Sieverling L, Hong C, Koser SD, Ginsbach P, Kleinheinz K et al.

    Nature communications 2020;11;1;733

  • Integrative pathway enrichment analysis of multivariate omics data.

    Paczkowska M, Barenboim J, Sintupisut N, Fox NS, Zhu H et al.

    Nature communications 2020;11;1;735

  • Pathway and network analysis of more than 2500 whole cancer genomes.

    Reyna MA, Haan D, Paczkowska M, Verbeke LPC, Vazquez M et al.

    Nature communications 2020;11;1;729

  • The evolutionary history of 2,658 cancers.

    Gerstung M, Jolly C, Leshchiner I, Dentro SC, Gonzalez S et al.

    Nature 2020;578;7793;122-128

  • The repertoire of mutational signatures in human cancer.

    Alexandrov LB, Kim J, Haradhvala NJ, Huang MN, Tian Ng AW et al.

    Nature 2020;578;7793;94-101

  • Analyses of non-coding somatic drivers in 2,658 cancer whole genomes.

    Rheinbay E, Nielsen MM, Abascal F, Wala JA, Shapira O et al.

    Nature 2020;578;7793;102-111

  • Pan-cancer analysis of whole genomes.

    ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium

    Nature 2020;578;7793;82-93

  • Patterns of somatic structural variation in human cancer genomes.

    Li Y, Roberts ND, Wala JA, Shapira O, Schumacher SE et al.

    Nature 2020;578;7793;112-121

  • Tobacco smoking and somatic mutations in human bronchial epithelium.

    Yoshida K, Gowers KHC, Lee-Six H, Chandrasekharan DP, Coorens T et al.

    Nature 2020;578;7794;266-272

  • Genomic evidence supports a clonal diaspora model for metastases of esophageal adenocarcinoma.

    Noorani A, Li X, Goddard M, Crawte J, Alexandrov LB et al.

    Nature genetics 2020;52;1;74-83

  • Embryonal precursors of Wilms tumor.

    Coorens THH, Treger TD, Al-Saadi R, Moore L, Tran MGB et al.

    Science (New York, N.Y.) 2019;366;6470;1247-1251

  • The landscape of somatic mutation in normal colorectal epithelial cells.

    Lee-Six H, Olafsson S, Ellis P, Osborne RJ, Sanders MA et al.

    Nature 2019;574;7779;532-537

  • Somatic mutations and clonal dynamics in healthy and cirrhotic human liver.

    Brunner SF, Roberts ND, Wylie LA, Moore L, Aitken SJ et al.

    Nature 2019;574;7779;538-542

  • Genomic landscape and chronological reconstruction of driver events in multiple myeloma.

    Maura F, Bolli N, Angelopoulos N, Dawson KJ, Leongamornlert D et al.

    Nature communications 2019;10;1;3835

  • Somatic evolution and global expansion of an ancient transmissible cancer lineage.

    Baez-Ortega A, Gori K, Strakova A, Allen JL, Allum KM et al.

    Science (New York, N.Y.) 2019;365;6452

  • Somatic mutation and clonal expansions in human tissues.

    Martincorena I

    Genome medicine 2019;11;1;35

  • Recurrent histone mutations in T-cell acute lymphoblastic leukaemia.

    Collord G, Martincorena I, Young MD, Foroni L, Bolli N et al.

    British journal of haematology 2019;184;4;676-679

  • Neutral tumor evolution?

    Tarabichi M, Martincorena I, Gerstung M, Leroi AM, Markowetz F et al.

    Nature genetics 2018;50;12;1630-1633

  • Somatic mutant clones colonize the human esophagus with age.

    Martincorena I, Fowler JC, Wabik A, Lawson ARJ, Abascal F et al.

    Science (New York, N.Y.) 2018;362;6417;911-917

  • An integrated genomic analysis of anaplastic meningioma identifies prognostic molecular signatures.

    Collord G, Tarpey P, Kurbatova N, Martincorena I, Moran S et al.

    Scientific reports 2018;8;1;13537

  • Population dynamics of normal human blood inferred from somatic mutations.

    Lee-Six H, Øbro NF, Shepherd MS, Grossmann S, Dawson K et al.

    Nature 2018;561;7724;473-478

  • Genomic patterns of progression in smoldering multiple myeloma.

    Bolli N, Maura F, Minvielle S, Gloznik D, Szalat R et al.

    Nature communications 2018;9;1;3363

  • Prediction of acute myeloid leukaemia risk in healthy individuals.

    Abelson S, Collord G, Ng SWK, Weissbrod O, Mendelson Cohen N et al.

    Nature 2018;559;7714;400-404

  • Cancer-mutation network and the number and specificity of driver mutations.

    Iranzo J, Martincorena I and Koonin EV

    Proceedings of the National Academy of Sciences of the United States of America 2018;115;26;E6010-E6019

  • Sequencing of prostate cancers identifies new cancer genes, routes of progression and drug targets.

    Wedge DC, Gundem G, Mitchell T, Woodcock DJ, Martincorena I et al.

    Nature genetics 2018;50;5;682-692

  • Pathway-based dissection of the genomic heterogeneity of cancer hallmarks' acquisition with SLAPenrich.

    Iorio F, Garcia-Alonso L, Brammeld JS, Martincorena I, Wille DR et al.

    Scientific reports 2018;8;1;6713

  • Timing the Landmark Events in the Evolution of Clear Cell Renal Cell Cancer: TRACERx Renal.

    Mitchell TJ, Turajlic S, Rowan A, Nicol D, Farmery JHR et al.

    Cell 2018;173;3;611-623.e17

  • Biological and prognostic impact of APOBEC-induced mutations in the spectrum of plasma cell dyscrasias and multiple myeloma cell lines.

    Maura F, Petljak M, Lionetti M, Cifola I, Liang W et al.

    Leukemia 2018;32;4;1044-1048

  • Universal Patterns of Selection in Cancer and Somatic Tissues.

    Martincorena I, Raine KM, Gerstung M, Dawson KJ, Haase K et al.

    Cell 2017;171;5;1029-1041.e21

  • The driver landscape of sporadic chordoma.

    Tarpey PS, Behjati S, Young MD, Martincorena I, Alexandrov LB et al.

    Nature communications 2017;8;1;890

  • Genomic Evolution of Breast Cancer Metastasis and Relapse.

    Yates LR, Knappskog S, Wedge D, Farmery JHR, Gonzalez S et al.

    Cancer cell 2017;32;2;169-184.e7

  • Recurrent mutation of IGF signalling genes and distinct patterns of genomic rearrangement in osteosarcoma.

    Behjati S, Tarpey PS, Haase K, Ye H, Young MD et al.

    Nature communications 2017;8;15936

  • Genome-wide chemical mutagenesis screens allow unbiased saturation of the cancer genome and identification of drug resistance mutations.

    Brammeld JS, Petljak M, Martincorena I, Williams SP, Alonso LG et al.

    Genome research 2017;27;4;613-625

  • Somatic mutations reveal asymmetric cellular dynamics in the early human embryo.

    Ju YS, Martincorena I, Gerstung M, Petljak M, Alexandrov LB et al.

    Nature 2017;543;7647;714-718

  • Precision oncology for acute myeloid leukemia using a knowledge bank approach.

    Gerstung M, Papaemmanuil E, Martincorena I, Bullinger L, Gaidzik VI et al.

    Nature genetics 2017;49;3;332-340

  • Mutational signatures associated with tobacco smoking in human cancer.

    Alexandrov LB, Ju YS, Haase K, Van Loo P, Martincorena I et al.

    Science (New York, N.Y.) 2016;354;6312;618-622

  • Tissue-specific mutation accumulation in human adult stem cells during life.

    Blokzijl F, de Ligt J, Jager M, Sasselli V, Roerink S et al.

    Nature 2016;538;7624;260-264

  • Genomic Classification and Prognosis in Acute Myeloid Leukemia.

    Papaemmanuil E, Gerstung M, Bullinger L, Gaidzik VI, Paschka P et al.

    The New England journal of medicine 2016;374;23;2209-2221

  • Landscape of somatic mutations in 560 breast cancer whole-genome sequences.

    Nik-Zainal S, Davies H, Staaf J, Ramakrishna M, Glodzik D et al.

    Nature 2016;534;7605;47-54

  • Constrained positive selection on cancer mutations in normal skin.

    Martincorena I, Jones PH and Campbell PJ

    Proceedings of the National Academy of Sciences of the United States of America 2016;113;9;E1128-9

  • Somatic mutation in cancer and normal cells.

    Martincorena I and Campbell PJ

    Science (New York, N.Y.) 2015;349;6255;1483-9

  • Tumor evolution. High burden and pervasive positive selection of somatic mutations in normal human skin.

    Martincorena I, Roshan A, Gerstung M, Ellis P, Van Loo P et al.

    Science (New York, N.Y.) 2015;348;6237;880-6

  • Origins and functional consequences of somatic mitochondrial DNA mutations in human cancer.

    Ju YS, Alexandrov LB, Gerstung M, Martincorena I, Nik-Zainal S et al.

    eLife 2014;3

  • Genome sequencing of normal cells reveals developmental lineages and mutational processes.

    Behjati S, Huch M, van Boxtel R, Karthaus W, Wedge DC et al.

    Nature 2014;513;7518;422-425

  • Mobile DNA in cancer. Extensive transduction of nonrepetitive DNA mediated by L1 retrotransposition in cancer genomes.

    Tubio JMC, Li Y, Ju YS, Martincorena I, Cooke SL et al.

    Science (New York, N.Y.) 2014;345;6196;1251343

  • Processed pseudogenes acquired somatically during cancer development.

    Cooke SL, Shlien A, Marshall J, Pipinikas CP, Martincorena I et al.

    Nature communications 2014;5;3644

  • Recurrent PTPRB and PLCG1 mutations in angiosarcoma.

    Behjati S, Tarpey PS, Sheldon H, Martincorena I, Van Loo P et al.

    Nature genetics 2014;46;4;376-379

  • RAG-mediated recombination is the predominant driver of oncogenic rearrangement in ETV6-RUNX1 acute lymphoblastic leukemia.

    Papaemmanuil E, Rapado I, Li Y, Potter NE, Wedge DC et al.

    Nature genetics 2014;46;2;116-25

  • Transmissible [corrected] dog cancer genome reveals the origin and history of an ancient cell lineage.

    Murchison EP, Wedge DC, Alexandrov LB, Fu B, Martincorena I et al.

    Science (New York, N.Y.) 2014;343;6169;437-440

  • Heterogeneity of genomic evolution and mutational profiles in multiple myeloma.

    Bolli N, Avet-Loiseau H, Wedge DC, Van Loo P, Alexandrov LB et al.

    Nature communications 2014;5;2997

  • Inactivating CUX1 mutations promote tumorigenesis.

    Wong CC, Martincorena I, Rust AG, Rashid M, Alifrangis C et al.

    Nature genetics 2014;46;1;33-8

  • Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2.

    Nangalia J, Massie CE, Baxter EJ, Nice FL, Gundem G et al.

    The New England journal of medicine 2013;369;25;2391-2405

  • Direct competition between hnRNP C and U2AF65 protects the transcriptome from the exonization of Alu elements.

    Zarnack K, König J, Tajnik M, Martincorena I, Eustermann S et al.

    Cell 2013;152;3;453-66

  • The genetic heterogeneity and mutational burden of engineered melanomas in zebrafish models.

    Yen J, White RM, Wedge DC, Van Loo P, de Ridder J et al.

    Genome biology 2013;14;10;R113

  • Evidence of non-random mutation rates suggests an evolutionary risk management strategy.

    Martincorena I, Seshasayee AS and Luscombe NM

    Nature 2012;485;7396;95-8

  • The organization of local and distant functional connectivity in the human brain.

    Sepulcre J, Liu H, Talukdar T, Martincorena I, Yeo BT and Buckner RL

    PLoS computational biology 2010;6;6;e1000808

Martincorena, Inigo
Inigo's Timeline
2018

Description of the mutational landscape of normal oesophagus.

2017

Description of universal patterns of selection in cancer and somatic tissues.

2016

Group Leader, Sanger Institute.

CRUK Career Development Fellow.

2015

Description of the mutational landscape of normal skin.

2013

Research Fellow, Queens' College, University of Cambridge.

Postdoctoral Fellow, Sanger Institute.

2012

PhD Evolutionary Genomics, University of Cambridge and EBI-EMBL.

2007

MSc Biochemistry, University of Navarra, Spain.

MSc Biology, University of Navarra, Spain.