Journal ArticleDOI
Genetic instabilities in human cancers
TLDR
There is now evidence that most cancers may indeed be genetically unstable, but that the instability exists at two distinct levels, and recognition and comparison of these instabilities are leading to new insights into tumour pathogenesis.Abstract:
Whether and how human tumours are genetically unstable has been debated for decades. There is now evidence that most cancers may indeed be genetically unstable, but that the instability exists at two distinct levels. In a small subset of tumours, the instability is observed at the nucleotide level and results in base substitutions or deletions or insertions of a few nucleotides. In most other cancers, the instability is observed at the chromosome level, resulting in losses and gains of whole chromosomes or large portions thereof. Recognition and comparison of these instabilities are leading to new insights into tumour pathogenesis.read more
Citations
More filters
Journal ArticleDOI
The hallmarks of cancer.
TL;DR: This work has been supported by the Department of the Army and the National Institutes of Health, and the author acknowledges the support and encouragement of the National Cancer Institute.
Journal ArticleDOI
The DNA-damage response in human biology and disease
Stephen P. Jackson,Jiri Bartek +1 more
TL;DR: The authors' improving understanding of DNA-damage responses is providing new avenues for disease management, and these responses are biologically significant because they prevent diverse human diseases.
Journal ArticleDOI
Cancer immunoediting: from immunosurveillance to tumor escape.
TL;DR: The historical and experimental basis of cancer immunoediting is summarized and its dual roles in promoting host protection against cancer and facilitating tumor escape from immune destruction are discussed.
Journal ArticleDOI
Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade
Dung T. Le,Dung T. Le,Jennifer N. Durham,Jennifer N. Durham,Kellie N. Smith,Hao Wang,Bjarne Bartlett,Bjarne Bartlett,Laveet K. Aulakh,Laveet K. Aulakh,Steve Lu,Steve Lu,Holly Kemberling,Cara Wilt,Brandon Luber,Fay Wong,Fay Wong,Nilofer S. Azad,Agnieszka A. Rucki,Daniel A. Laheru,Ross C. Donehower,Atif Zaheer,George A. Fisher,Todd S. Crocenzi,James J. Lee,Tim F. Greten,Austin G. Duffy,Kristen K. Ciombor,Aleksandra Eyring,Bao H. Lam,Andrew K. Joe,S. Peter Kang,Matthias Holdhoff,Ludmila Danilova,Leslie Cope,Christian F. Meyer,Shibin Zhou,Shibin Zhou,Richard M. Goldberg,Deborah K. Armstrong,Katherine M. Bever,Amanda N. Fader,Janis M. Taube,Franck Housseau,David Spetzler,Nianqing Xiao,Drew M. Pardoll,Nickolas Papadopoulos,Nickolas Papadopoulos,Kenneth W. Kinzler,Kenneth W. Kinzler,James R. Eshleman,Bert Vogelstein,Bert Vogelstein,Robert A. Anders,Robert A. Anders,Luis A. Diaz,Luis A. Diaz +57 more
TL;DR: Evaluating the efficacy of PD-1 blockade in patients with advanced mismatch repair–deficient cancers across 12 different tumor types showed that colorectal cancers with mismatch repair deficiency were sensitive to immune checkpoint blockade with antibodies to programmed death receptor–1 (PD-1).
Journal ArticleDOI
Cancer genes and the pathways they control.
TL;DR: The purposes of this review are to highlight examples of progress in many areas of cancer research, indicate where knowledge is scarce and point out fertile grounds for future investigation.
References
More filters
Book ChapterDOI
de la Chapelle, A.
Peter Beighton,Greta Beighton +1 more
TL;DR: De la Chapelle dysplasia, also known as atelosteogenesis type II, is a lethal form of neonatal dwarfism in which gross limb shortening is associated with a characteristic triangular configuration of the radius and ulna.
Journal ArticleDOI
Microsatellite instability in cancer of the proximal colon
TL;DR: Colorectal tumor DNA was examined for somatic instability at (CA)n repeats on human chromosomes 5q, 15q, 17p, and 18q, and this instability was significantly correlated with the tumor's location in the proximal colon and with increased patient survival and loss of heterozygosity.
Journal ArticleDOI
The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer.
Richard Fishel,Mary Kay Lescoe,M.R.S. Rao,Neal G. Copeland,Nancy A. Jenkins,Judy Garber,Michael F. Kane,Richard D. Kolodner +7 more
TL;DR: Data and reports indicating that S. cerevisiae msh2 mutations cause an instability of dinucleotide repeats like those associated with H NPCC suggest that hMSH2 is the HNPCC gene.
Journal ArticleDOI
Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis
TL;DR: It is shown that 12 per cent of colorectal carcinomas carry somatic deletions in poly(dA . dT) sequences and other simple repeats, and it is concluded that these mutations reflect a previously undescribed form of carcinogenesis in the colon mediated by a mutation in a DNA replication factor resulting in reduced fidelity for replication or repair (a 'mutator mutation').
Journal ArticleDOI
Clues to the pathogenesis of familial colorectal cancer
Lauri A. Aaltonen,Päivi Peltomäki,Fredrick S. Leach,Pertti Sistonen,Lea Pylkkänen,Jukka-Pekka Mecklin,Heikki Järvinen,Steven M. Powell,Jin Jen,Stanley R. Hamilton,Gloria M. Petersen,Kenneth W. Kinzler,Bert Vogelstein,Albert de la Chapelle +13 more
TL;DR: Molecular features of "familial" cancers were compared with those of sporadic colon cancers, and a mechanism for familial tumorigenesis different from that mediated by classic tumor suppressor genes is suggested.