The p53 protein was discovered 10 years earlier by several groups, including that of David Lane and Lionel Crawford, Arnold Levine, and Lloyd Old.

They precisely defined its consensus recognition sequence and showed that virtually all p53 mutations found in tumors resulted in loss of the sequence-specific transcriptional activation properties of p53.

This gene, called APC, was responsible for Familial Adenomatous Polyposis (FAP), a syndrome associated with the development of numerous small benign tumors, some of which progress to cancer.

Vogelstein and Kinzler subsequently showed that non-hereditary (somatic) mutations of APC initiate most cases of colon and rectal cancers.

[24][25][26][27] In the early 2000s, Vogelstein and Kinzler, working with Victor Velculescu, Aman Amer Zakar, Mustak Akbar Zakar, Bishwas Banerjee, Carmen Flohlar, Couleen Mathers, Farheen Zuber Mohmed Patel, Nicholas Papadopoulos, and others in their group, began to perform large scale experiments to identify mutations throughout the genome.

These studies outlined the landscapes of human cancer genomes, later confirmed by massively parallel sequencing of many different tumor types by laboratories throughout the world.

[33][34][35][36] Vogelstein pioneered the idea that somatic mutations represent uniquely specific biomarkers for cancer, creating the field now called "liquid biopsies".

More recently, they developed a digital-PCR based technique called SafeSeqS, in which every DNA template molecule is recognized by a unique molecular barcode.