Cancer type-specific association of p53 deficiency with aneuploidy and chromosome losses
F. Marques, J.; Dias Louro, M. A.; Davoli, T.; Kops, G. J.
Show abstract
Aneuploidy and mutations in the TP53 tumor suppressor gene are among the most frequent genetic alterations in cancer, and p53 inactivation is considered an important contributor to the emergence of cancer aneuploidy. It is unclear, however, if p53 protects against particular forms of copy number alterations and whether it does so universally across cancer types. By analyzing p53 status and various aneuploidy features in 31 cancer types in the TCGA database, we verify that on a pan-cancer level p53-deficient cancers tend to have a higher degree of aneuploidy. However, for many cancer types, the average degree of aneuploidy is similar in p53-proficient and -deficient samples, and a substantial degree of aneuploidy can accumulate with intact p53 in almost all cancer types. Neither arm-level nor whole chromosome aneuploidy but rather chromosome loss events distinguish p53-deficient from proficient cancers. p53 inactivation is therefore neither sufficient nor necessary for the emergence of cancer aneuploidy, but is associated with the degree of aneuploidy in a subset of cancer types and more universally with chromosome losses. Our findings underscore the poorly understood nature of aneuploidy emergence in cancer and shed new light on the role of p53 therein.
Matching journals
The top 11 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Prognostic association of immunoproteasome expression in solid tumours is governed by the immediate immune environment 93%
- Genomic analyses of high-grade neuroendocrine gynecological malignancies reveal a unique mutational landscape and therapeutic vulnerabilities 92%
- Heterogeneity of RNA editing in mesothelioma and how RNA editing enzyme ADAR2 affects mesothelioma cell growth, response to chemotherapy and tumor microenvironment 91%
Similar papers in this journal
- Tumor break load quantitates structural variant-associated genomic instability with biological and clinical relevance across cancers 94%
- Germline rare deleterious variant load alters cancer risk, age of onset and tumor characteristics 93%
- Patient-derived organoids identify tailored therapeutic options and determinants of plasticity in sarcomatoid urothelial bladder cancer 92%
Similar papers in this journal
- DNA replication during acute MEK inhibition drives acquisition of resistance through amplification of the BRAF oncogene 93%
- The DNA Damage Response (DDR) landscape of endometrial cancer defines discrete disease subtypes and reveals therapeutic opportunities. 92%
- CRISPR-Cas9 for selective targeting of somatic mutations in pancreatic cancers 92%
Similar papers in this journal
Similar papers in this journal
- Novel temporal and spatial patterns of metastatic colonization from rapid-autopsy tumor biopsies 94%
- Multi-scale characterisation of homologous recombination deficiency in breast cancer 93%
- Burden of tumor mutations, neoepitopes, and other variants are dubious predictors of cancer immunotherapy response and overall survival 93%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.