hotspot
Meaning of hotspot: Recurrence is what makes them useful, since a change seen repeatedly at one position is easier to test for and interpret.
Definition of hotspot
A hotspot is a place in the genome where a particular event happens far more often than in the surrounding DNA. Most often the event is mutation: certain sequences and structures are prone to being misread while being copied, or repaired incorrectly afterward, so the same change recurs at the same position in unrelated people.
What makes a site a hotspot?
Chemistry accounts for much of it. A cytosine carrying a methyl tag, which is common where a cytosine sits next to a guanine, slowly converts to thymine on its own, and if repair misses it the change becomes permanent. Ultraviolet light fuses neighboring pyrimidine bases, so skin cells accumulate mutation at those pairs. Stretches of repeated letters cause the copying machinery to slip, adding or dropping units, and unusual folded structures stall the machinery during DNA replication, leaving errors behind. Regions that are copied late, or that are tightly packed and less accessible to repair enzymes, collect more damage than open, early copied regions.
Why do hotspots matter in cancer?
| Kind of hotspot | What recurs there |
|---|---|
| Mutation hotspot | The same base change, in unrelated tumors or families |
| Recombination hotspot | Chromosome crossovers during the making of eggs and sperm |
| Fragile site | Breaks and rearrangements of the chromosome |
Recurrence in tumors is not chemistry alone. A position looks hot partly because a change there gives the cell an advantage and is therefore selected for and kept, while equally frequent changes elsewhere are discarded. Certain positions within a single gene recur again and again across thousands of tumors for that reason. Because those positions are known in advance, laboratories can test a short stretch of sequence rather than an entire gene, and the meaning of a result at a well documented position is far clearer than the meaning of a change never seen before.
Does the word mean anything else?
It does, and the senses are unconnected. In nuclear medicine imaging, a hot spot is an area on a bone scan or a positron emission tomography image where the injected tracer has gathered more densely than in surrounding tissue, indicating higher activity there. The context makes the meaning plain: a hotspot in a genetics report is a position in a sequence, while a hot spot on a scan is a place in the body.
Used in a sentence
Genetic testing identified a mutation at a known hotspot within the gene of interest.
Good to know
A mutation occurring at a known hotspot is not automatically more harmful than one elsewhere in the same gene, since the effect of any change still depends on how it alters the resulting protein.