Exon 14

To paraphrase "GPs Behind Closed Doors", this post contains challenging medical issues.

Exon 14 sounds like a science fiction film. As little as ten years ago, it could well have been, but actually it is real.

I have something called the MET Exon 14 skipping mutation. It alters a specific gene, the MET gene (mesenchymal-epithelial transition) so that affected cells produce an abnormal protein which makes them grow uncontrollably.

The mutation causes lung tumours. It affects mainly smokers, but I put mine down to dirty Leeds in the nineteen-seventies when large numbers smoked, and offices, buses, cinemas, pubs and the shared houses I lived in reeked of a blue haze that stuck to your hair and clothes so much that you failed to notice. Leeds was also full of traffic fumes and pollution from coal fires and industries, and my accountancy job involved hours walking round warehouses, mills and factories where there were all kinds of dust and chemical vapours. The cause on my health record is "significant passive smoking". 

I was entirely symptomless until I had a seizure. Perhaps a routine chest X-ray might have detected it sooner and saved me a lot of trouble, but it was as good as impossible to get one during the covid lockdown, even if I had thought to request one.

Diagnosis begins with a CT-directed lung biopsy. You lie face-down in a CT scanner while a surgeon positions a thing metal tube into your back, through which they can then cut out and remove a small piece of tumour tissue for analysis and gene-sequencing. It is not a comfortable procedure. I wondered what was the cold liquid running into the back of my throat, which I had to spit out on to the scanner table. It was blood. We don't normally realise how cold the insides of our lungs get.

Gene sequencing is only the first part of the science fiction. There is a targeted therapy. The Merck drug company have licenced a chemical called Tepotinib (trade mane Tepmetko) in the form of a daily pill that blocks the abnormal protein, and slows down or stops the tumours from growing. It is a high cost treatment; I have heard a figure of £7,000 per month mentioned, but thanks to the NHS I do not have to pay.

Surprisingly, it is a relatively simple chemical - a hydrochloride hydrate of C₂₉H₂₈N₆O₂. I imagine that in some parts of the world they ignore the patent and make it themselves for a few pence per pill.

I have had other treatments too: chemotherapy which was awful, lung radiotherapy which was little trouble in my case, gamma knife radiotherapy which pinpoints and zaps small brain metastases, a brain op to drain the cyst that gamma knife left behind, which was scary. All over a year ago.

The side effects of Tepotinib are difficult, especially oedema (fluid retention). If you get cold it takes ages to get warm again because it is the equivalent of having 20 pounds (9 kg) of cold water bags strapped around your limbs and body, and, believe me, you would not want to have scrotal oedema (or vulval oedema I imagine, but don't know because I don't have that).

I am OK. It is but a scratch. I've had worse. None shall pass. I am still here.  

So, not only have we mapped the human genome to identify the 25,000 or so genes of our 23 chromosomes, we can gene-sequence malfunctioning cells to pick out a defective gene, understand its mechanisms, and construct a chemical to block its actions. To those of my generation, even the technologically literate, that really does sound like science fiction.

New things like this are coming along all the time. It should give hope to those who might become ill in the future.