MLH1

The seventh area that we look at is DNA protection and repair, and this is the one people understand least, and I think it's quietly one of the most important.

The TP53, the tumor suppressor, sometimes called the guardian of the genome, And then there's ATM, MLH1, MDM2, XRCC3, plus the antioxidant genes that we talked about before, those combination of three.

SOD2, SOD3, GPX1 and catalase.

And what this section tells you is how well your cells repair the damage that happens to them every single day and how well you mop up the oxidative stress that can cause the damage in the first place.

And sometimes I'm discussing biomarkers that are clinically impacting my decision-making that day.

But many times there's a bunch of biomarkers listed that have nothing to do with our conversation that day, but I still feel obligated that I should mention that they have a mismatch repair deficiency that's from MLH1 methylation, even though it's not hereditary.

I'm not going to make any decision making, but I should mention it.

And maybe in the future it could be impactful.

Surgery and pathology confirmed that it was recurrent colorectal cancer.

Immunohistochemistry staining showed loss of MLH1 and PMS2, which suggested a mismatched repair deficiency.

This was our first important clue.

Then we ran a CGP on the tissue that identified a deleterious POLD1 alteration.

So what did they do? Sarah.

First, they validated antibodies for feline MLH1, MSH2, and MSH6 proteins using CRISPR-engineered cell lines.

A very solid approach.

They then used immunohistochemistry to screen 83 feline tumors for expression of these proteins.

And the findings? Well.

Sarah, they found loss of expression in several tumor types.

Most notably, MLH1 expression was lost in 100% of melanomas and 93% of osteosarcomas.

Alex, that's actually quite striking, even for a pilot study.