Bert Vogelstein

A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity

Stem cell divisions, somatic mutations, cancer etiology, and cancer prevention

A substantial fraction of mutations in human cancer are attributable to random errors occurring during DNA replication.

High Frequency of Mutations of the <i>PIK3CA</i> Gene in Human Cancers

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Mutational Analysis of the Tyrosine Kinome in Colorectal Cancers

Tyrosine kinases (TKs) are central regulators of signaling pathways that control differentiation, transcription, cell cycle progression, apoptosis, motility, and invasion ( [1][...

A model for p53-induced apoptosis

PD-1 Blockade in Tumors with Mismatch-Repair Deficiency

This study showed that mismatch-repair status predicted clinical benefit of immune checkpoint blockade with pembrolizumab. (Funded by Johns Hopkins University and others; Clinic...

Incidence and functional consequences of <i>hMLH1</i> promoter hypermethylation in colorectal carcinoma

Inactivation of the genes involved in DNA mismatch repair is associated with microsatellite instability (MSI) in colorectal cancer. We report that hypermethylation of the 5′ CpG...

Epitope Landscape in Breast and Colorectal Cancer

Abstract The finding that individual cancers contain many mutant genes not present in normal tissues has prompted considerable interest in the cancer epitope landscape. To furth...

Cancer Genome Landscapes

Over the past decade, comprehensive sequencing efforts have revealed the genomic landscapes of common forms of human cancer. For most cancer types, this landscape consists of a ...

Chromosome 17 Deletions and p53 Gene Mutations in Colorectal Carcinomas

Previous studies have demonstrated that allelic deletions of the short arm of chromosome 17 occur in over 75% of colorectal carcinomas. Twenty chromosome 17p markers were used t...

The Consensus Coding Sequences of Human Breast and Colorectal Cancers

The elucidation of the human genome sequence has made it possible to identify genetic alterations in cancers in unprecedented detail. To begin a systematic analysis of such alte...

The Genomic Landscapes of Human Breast and Colorectal Cancers

Human cancer is caused by the accumulation of mutations in oncogenes and tumor suppressor genes. To catalog the genetic changes that occur during tumorigenesis, we isolated DNA ...

Clues to the Pathogenesis of Familial Colorectal Cancer

A predisposition to colorectal cancer is shown to be linked to markers on chromosome 2 in some families. Molecular features of "familial" cancers were compared with those of spo...

Somatic mutations in the chromatin remodeling gene <i>ARID1A</i> occur in several tumor types

Mutations in the chromatin remodeling gene ARID1A have recently been identified in the majority of ovarian clear cell carcinomas (OCCCs). To determine the prevalence of mutation...

p53 Mutations in Human Cancers

Mutations in the evolutionarily conserved codons of the p53 tumor suppressor gene are common in diverse types of human cancer. The p53 mutational spectrum differs among cancers ...

Definition of a consensus binding site for p53

Suppression of Human Colorectal Carcinoma Cell Growth by Wild-Type p53

Mutations of the p53 gene occur commonly in colorectal carcinomas and the wild-type p53 allele is often concomitantly deleted. These findings suggest that the wild-type gene may...

Identification of p53 as a Sequence-Specific DNA-Binding Protein

The tumor-suppressor gene p53 is altered by missense mutation in numerous human malignancies. However, the biochemical properties of p53 and the effect of mutation on these prop...

Oncogenic Forms of p53 Inhibit p53-Regulated Gene Expression

Mutant forms of the gene encoding the tumor suppressor p53 are found in numerous human malignancies, but the physiologic function of p53 and the effects of mutations on this fun...

Whole genome PCR: application to the identification of sequences bound by gene regulatory protein

A strategy is described that allows the isolation of DNA sequences that can bind to gene regulatory proteins. Total genomic DNA is first converted to a form that is suitable for...

Scrambled exons

Top-down morphogenesis of colorectal tumors

One of the fundamental tenets of oncology is that tumors arise from stem cells. In the colon, stem cells are thought to reside at the base of crypts. In the early stages of tumo...

Cancer-Specific High-Throughput Annotation of Somatic Mutations: Computational Prediction of Driver Missense Mutations

Abstract Large-scale sequencing of cancer genomes has uncovered thousands of DNA alterations, but the functional relevance of the majority of these mutations to tumorigenesis is...

Surfing the p53 network

A genetic model for colorectal tumorigenesis

An Integrated Genomic Analysis of Human Glioblastoma Multiforme

Glioblastoma multiforme (GBM) is the most common and lethal type of brain cancer. To identify the genetic alterations in GBMs, we sequenced 20,661 protein coding genes, determin...

Core Signaling Pathways in Human Pancreatic Cancers Revealed by Global Genomic Analyses

There are currently few therapeutic options for patients with pancreatic cancer, and new insights into the pathogenesis of this lethal disease are urgently needed. Toward this e...

Distant metastasis occurs late during the genetic evolution of pancreatic cancer

Gatekeepers and caretakers

Accumulation of driver and passenger mutations during tumor progression

Major efforts to sequence cancer genomes are now occurring throughout the world. Though the emerging data from these studies are illuminating, their reconciliation with epidemio...

Comparative lesion sequencing provides insights into tumor evolution

We show that the times separating the birth of benign, invasive, and metastatic tumor cells can be determined by analysis of the mutations they have in common. When combined wit...

Half or more of the somatic mutations in cancers of self-renewing tissues originate prior to tumor initiation

Although it has been hypothesized that some of the somatic mutations found in tumors may occur before tumor initiation, there is little experimental or conceptual data on this t...

Design and analysis issues in genome-wide somatic mutation studies of cancer