The vast majority of recurrent somatic mutations arising in tumors affect protein-coding genes in the nuclear genome. Here, through population-scale analysis of 14,106 whole tumor genomes, we report the discovery of highly recurrent mutations affecting both the small (12S, MT-RNR1) and large (16S, MT-RNR2) mitochondrial RNA subunits of the mitochondrial ribosome encoded within mitochondrial DNA (mtDNA). Compared...Read More

Genetic similarity of populations (or genetic ancestry) is associated with differences in somatic alterations in cancers. We meta-analyze two targeted panel sequencing cohorts with 275,605 samples from 14 cancer types. Here we find a recurrent depletion of TERT promoter mutations in patients of African and East Asian ancestry across multiple cancers. Several clinically actionable alterations, such as ERBB2 mutations...Read More

MSK is a founding member of the Cancer AI Alliance (CAIA), an exciting collaborative research initiative designed to accelerate development and deployment of AI models to improve cancer care.   This unique alliance unites four leading NCI-designated cancer centers — MSK, Dana-Farber Cancer Institute, Fred Hutch Cancer Center, and The Sidney Kimmel Comprehensive Cancer Center and...Read More

A new study led by researchers at Memorial Sloan Kettering Cancer Center (MSK) offers critical insights into how high-grade serous ovarian carcinoma — the most common and aggressive form of ovarian cancer — evolves. Published July 16 in Nature, the study used single-cell sequencing to explore a process called whole-genome doubling (WGD), in which cancer...Read More

Whole-genome doubling (WGD) is a common feature of human cancers and is linked to tumour progression, drug resistance, and metastasis1,2,3,4,5,6. Here we examine the impact of WGD on somatic evolution and immune evasion at single-cell resolution in patient tumours. Using single-cell whole-genome sequencing, we analysed 70 high-grade serous ovarian cancer samples from 41 patients (30,260...Read More

Obesity is a risk factor for cancer, but whether obesity is linked to specific genomic subtypes of cancer is unknown. We examined the relationship between obesity and tumor genotype in two clinicogenomic corpora. Obesity was associated with specific driver mutations in lung adenocarcinoma, endometrial carcinoma and cancers of unknown primaries, independent of clinical covariates, demographic...Read More

The digitization of health records and growing availability of tumour DNA sequencing provide an opportunity to study the determinants of cancer outcomes with unprecedented richness. Patient data are often stored in unstructured text and siloed datasets. Here we combine natural language processing annotations1,2 with structured medication, patient-reported demographic, tumour registry and tumour genomic data from 24,950...Read More

Dr. Adam Weiner published the paper Inferring replication timing and proliferation dynamics from single-cell DNA sequencing data. The study explores how dysregulated DNA replication is a cause and a consequence of aneuploidy in cancer, yet the interplay between copy number alterations (CNAs), replication timing (RT) and cell cycle dynamics remain understudied in aneuploid tumors. We...Read More

Dr. Nicholas Ceglia et al. published the paper Identification of transcriptional programs using dense vector representations defined by mutual information with GeneVector. A scalable framework for dimensionality reduction, GeneVector identifies transcriptional programs and classifies cell types. You can read the paper in Nature Communications here.Read More

Dr. Elli Papaemmanuil et al. published the paper Clonal evolution during metastatic spread in high-risk neuroblastoma. Patients with high-risk neuroblastoma generally present with widely metastatic disease and often relapse despite intensive therapy. As most studies to date focused on diagnosis-relapse pairs, our understanding of the genetic and clonal dynamics of metastatic spread and disease progression...Read More