Iñigo Martincorena
A5020879914- Cancer Genomics and Diagnostics
- Evolution and Genetic Dynamics
- Genetic factors in colorectal cancer
- Epigenetics and DNA Methylation
- Genomics and Phylogenetic Studies
- CRISPR and Genetic Engineering
- DNA Repair Mechanisms
- Genomics and Rare Diseases
- Acute Myeloid Leukemia Research
- Single-cell and spatial transcriptomics
- Bladder and Urothelial Cancer Treatments
- SARS-CoV-2 and COVID-19 Research
- Bioinformatics and Genomic Networks
- Prostate Cancer Diagnosis and Treatment
- Prostate Cancer Treatment and Research
- Genomics and Chromatin Dynamics
- Chromosomal and Genetic Variations
- Genomic variations and chromosomal abnormalities
- Cancer Research and Treatments
- Sarcoma Diagnosis and Treatment
- Renal and related cancers
- Pancreatic function and diabetes
- Multiple Myeloma Research and Treatments
- RNA Research and Splicing
- Myeloproliferative Neoplasms: Diagnosis and Treatment
Wellcome Sanger Institute
2016-2025
Imperial College London
2022
Quadram Institute
2022
Discovery Institute
2022
Sanford Burnham Prebys Medical Discovery Institute
2022
Addenbrooke's Hospital
2019-2022
Genomics (United Kingdom)
2022
ORCID
2021
Cambridge University Hospitals NHS Foundation Trust
2019
The Francis Crick Institute
2015-2017
Recent studies have provided a detailed census of genes that are mutated in acute myeloid leukemia (AML). Our next challenge is to understand how this genetic diversity defines the pathophysiology AML and informs clinical practice.
Abstract Somatic mutations in cancer genomes are caused by multiple mutational processes, each of which generates a characteristic signature 1 . Here, as part the Pan-Cancer Analysis Whole Genomes (PCAWG) Consortium 2 International Cancer Genome (ICGC) and The Atlas (TCGA), we characterized signatures using 84,729,690 somatic from 4,645 whole-genome 19,184 exome sequences that encompass most types cancer. We identified 49 single-base-substitution, 11 doublet-base-substitution, 4...
Somatic mutations in the Janus kinase 2 gene (JAK2) occur many myeloproliferative neoplasms, but molecular pathogenesis of neoplasms with nonmutated JAK2 is obscure, and diagnosis these remains a challenge.
How somatic mutations accumulate in normal cells is central to understanding cancer development but poorly understood. We performed ultradeep sequencing of 74 genes small (0.8 4.7 square millimeters) biopsies skin. Across 234 sun-exposed eyelid epidermis from four individuals, the burden averaged two six per megabase cell, similar that seen many cancers, and exhibited characteristic signatures exposure ultraviolet light. Remarkably, multiple are under strong positive selection even...
Cancer develops as a result of somatic mutation and clonal selection, but quantitative measures selection in cancer evolution are lacking. We adapted methods from molecular applied them to 7,664 tumors across 29 types. Unlike species evolution, positive outweighs negative during development. On average, <1 coding base substitution/tumor is lost through with purifying almost absent outside homozygous loss essential genes. This allows exome-wide enumeration all driver mutations, including...
The mutational burden of aging As people age, they accumulate somatic mutations in healthy cells. About 25% cells normal, sun-exposed skin harbor cancer driver mutations. What about tissues not exposed to powerful mutagens like ultraviolet light? Martincorena et al. performed targeted gene sequencing normal esophageal epithelium from nine human donors varying age (see the Perspective by Chanock). mutation rate was lower esophagus than skin, but there a strong positive selection clones...
Cancer develops through a process of somatic evolution
Multiple myeloma is an incurable plasma cell malignancy with a complex and incompletely understood molecular pathogenesis. Here we use whole-exome sequencing, copy-number profiling cytogenetics to analyse 84 samples. Most cases have subclonal structure show clusters of variants, including driver mutations. Serial sampling reveals diverse patterns clonal evolution, linear differential response branching evolution. Diverse processes contribute the mutational repertoire, kataegis somatic...
Abstract A key mutational process in cancer is structural variation, which rearrangements delete, amplify or reorder genomic segments that range size from kilobases to whole chromosomes 1–7 . Here we develop methods group, classify and describe somatic variants, using data the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium International Cancer Genome (ICGC) The Atlas (TCGA), aggregated whole-genome sequencing 2,658 cancers across 38 tumour types 8 Sixteen signatures variation...
Patterns of genomic evolution between primary and metastatic breast cancer have not been studied in large numbers, despite patients with having dismal survival. We sequenced whole genomes or a panel 365 genes on 299 samples from 170 locally relapsed cancer. Several lines analysis indicate that clones seeding metastasis relapse disseminate late tumors, but continue to acquire mutations, mostly accessing the same mutational processes active tumor. Most distant metastases acquired driver...
Chromothripsis is a mutational phenomenon characterized by massive, clustered genomic rearrangements that occurs in cancer and other diseases. Recent studies selected types have suggested chromothripsis may be more common than initially inferred from low-resolution copy-number data. Here, as part of the Pan-Cancer Analysis Whole Genomes (PCAWG) Consortium International Cancer Genome (ICGC) The Atlas (TCGA), we analyze patterns across 2,658 tumors 38 using whole-genome sequencing We find...
Clear cell renal carcinoma (ccRCC) is characterized by near-universal loss of the short arm chromosome 3, deleting several tumor suppressor genes. We analyzed whole genomes from 95 biopsies across 33 patients with clear carcinoma. find hotspots point mutations in 5′ UTR TERT, targeting a MYC-MAX-MAD1 repressor associated telomere lengthening. The most common structural abnormality generates simultaneous 3p and 5q gain (36% patients), typically through chromothripsis. This event occurs...
There are ∼650,000 Alu elements in transcribed regions of the human genome. These contain cryptic splice sites, so they constant danger aberrant incorporation into mature transcripts. Despite posing a major threat to transcriptome integrity, little is known about molecular mechanisms preventing their inclusion. Here, we present mechanism for protecting from exonization transposable elements. Quantitative iCLIP data show that RNA-binding protein hnRNP C competes with splicing factor U2AF65 at...
Information processing in the human brain arises from both interactions between adjacent areas and distant projections that form distributed systems. Here we map across different spatial scales by estimating degree of intrinsic functional connectivity for local (≤14 mm) neighborhood directly surrounding regions as contrasted with (>14 interactions. The balance measured at rest forms a separates sensorimotor cortices heteromodal association further identifies possess high cortical-cortical...
Intra-tumor heterogeneity (ITH) is a mechanism of therapeutic resistance and therefore an important clinical challenge. However, the extent, origin, drivers ITH across cancer types are poorly understood. To address this, we extensively characterize whole-genome sequences 2,658 samples spanning 38 types. Nearly all informative (95.1%) contain evidence distinct subclonal expansions with frequent branching relationships between subclones. We observe positive selection driver mutations most...