EML4-ALK lung cancer inv(2)
46,XY,inv(2)(p21p23)
Also known as: EML4-ALK, ALK-positive lung cancer, ALK rearrangement, inv(2)
46,XY,inv(2)(p21p23) is the paracentric inversion behind ALK-positive lung cancer, fusing EML4 with ALK within the short arm of chromosome 2. Typically found in younger patients and never or light smokers, it is the target of crizotinib and the ALK inhibitors that followed.
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What banding sees: The inversion within 2p is far too small to see with banding, so ALK-positive lung cancer is diagnosed by FISH, immunohistochemistry or sequencing rather than by a karyotype. The drawing above shows where the missing segment lies, not what would be visible down a microscope.
What the notation means
46 is the number of chromosomes counted in the cell. That is the normal number: 22 pairs of autosomes, the chromosomes other than X and Y, plus one pair of sex chromosomes. XY lists the sex chromosomes, here one X and one Y, the usual male set. These two fields open every karyotype because they describe the whole cell. Any abnormality is written after them.
An INVERSION (inv): a segment turned end for end within its chromosome. (2) refers to chromosome 2, the chromosome the inversion is on. One chromosome is listed, so one group of breakpoints follows, because each chromosome listed gets a group of its own. (p21p23) gives two breakpoints on the same arm, 2p21 and 2p23, listed in the order they sit on the chromosome, from the tip of the short arm toward the tip of the long arm. Because both are on the short arm, the flipped segment does not include the centromere. That is called a paracentric inversion.
Clinical notes
inv(2)(p21p23), EML4::ALK lung adenocarcinoma
EML4::ALK. When found in tumor tissue, this inversion means ALK-positive non-small cell lung cancer, typically adenocarcinoma in younger patients and never or light smokers, and it is treatable with crizotinib and the ALK inhibitors after it. The inversion hides in a normal-looking chromosome 2 not because of its size, since EML4 and ALK sit about 12 Mb apart, but because the flipped segment is mostly the dark band 2p22 with thin pale edges from 2p23 and 2p21, so it reads light, dark, light in either orientation. In practice it is a FISH, immunohistochemistry or sequencing finding, and the notation is taught rather than observed. The same ALK is the t(2;5) partner in anaplastic large cell lymphoma.