R2platform Data Science Annals

  Introduction In 1978, Edward Lewis described fruit flies with legs sprouting from their heads where antennae should be. The culprit was a mutated Hox gene — one of a conserved set of master regulators that tell every cell in a developing animal where it is in the body and what it should become. The discovery earned Lewis a Nobel Prize, and the gene family its name. Decades later, those same genes are drawing attention in oncology — not for growing legs in the wrong place, but for something arguably more dangerous: hijacking the developmental logic of human tumours. In humans, the HOX family comprises 39 genes arranged in four clusters — HOXA, HOXB, HOXC, and HOXD — spread across chromosomes 7, 17, 12, and 2 respectively. Their arrangement is not accidental. The genes are expressed in the same order along the chromosome as they are along the head-to-tail body axis during development. This principle — known as collinearity — is one of the most striking examples of genome organis...

T ags: gene families, transcription factors, neuroblastoma, MYCN They switch on growth. They are amplified in tumours. And for decades they were called undruggable. Few gene families are as closely tied to cancer as the MYC family. Its three members, MYC , MYCN and MYCL , encode transcription factors that tell a cell when to grow, divide and build the biomass to do so. When that signal gets stuck on, the consequences are severe. What the MYC proteins do All three share a basic helix-loop-helix leucine zipper (bHLH-LZ) domain. To work, they pair up with a partner protein called MAX, and the MYC–MAX dimer binds E-box sequences (CACGTG) in DNA. From there it regulates a large programme of genes involved in ribosome biogenesis, metabolism, protein synthesis and cell cycle progression. MYC is less a single-target switch than an amplifier of the cell’s existing growth programme. Three siblings, three territories MYC is broadly expressed in proliferating cells and is deregulated in m...