The G12D mutation results in an amino acid substitution at position 12 in KRAS, from a glycine (G) to an aspartic acid (D).https://www.mycancergenome.org/content/ ... r/kras/34/
rachel2017 wrote: NHMike wrote:For most patients, adoptive cell transfer starts with an operation at the National Cancer Institute. By removing one of your tumors, we are able to find and grow the immune cells that live there, known as tumor-infiltrating lymphocytes or TIL. We will grow and study TIL from your tumor in our labs.
With your permission, our referral team may request samples of your tumor to test for certain proteins of interest. For cancers expressing those proteins, patients with certain blood typing (HLA) can be treated without the need for an operation. We perform a large blood collection (called an apheresis) and genetically engineer your white blood cells to recognize those targets.https://ccr.cancer.gov/sb-faqs
I had thought that NCI was only dealing with folks with KRAS G12D with the HLA-C*0802 or HLA-A*1101 Alleles and maybe G12V in the future. But the text above on their site implies that they will take the cases of folks outside of this relatively small group of people as well. I suspect that they are trying to find other combinations where other Alleles express tumor cells of other kinds gene mutations. If my interpretation is correct, then it should be interesting that they are looking for cures for other mutations and finding them could provide hope for many more people. I do not know if they will find other combinations but I would expect that they would.
If I'm incorrect, please let me know. If there are those in the trial that don't have KRAS G12D or don't have HLA-C*0802 and HLA-A*1101, then that would be evidence that they are working on other mutations which would be exciting.
Hey, Mike, Thanks for your explanation. Now I have better understanding about Dr Jimmy Yang’s trial. My question is my mom have KRAS mutation: Gly12Asp. What kind of mutation is it? Is this differencing from G12D? Thanks in advanced!
So yes, G12D.
From MGH's page: https://targetedcancercare.massgeneral. ... D-(c-35G-A
KRAS is a gene that provides the code for making a protein, KRAS, which is involved primarily in controlling cell division. This protein is part of the MAP kinase signaling cascade (RAS/RAF/MEK/ERK) that relays chemical signals from outside the cell to the cell's nucleus and is primarily involved in controlling cell division. KRAS is an enzyme (a GTPase) that converts a molecule called GTP into GDP. When KRAS is attached (bound) to GDP, it's in its "off" position and can't send signals to the nucleus. But when a GTP molecule arrives and binds to KRAS, KRAS is activated and sends its signal, and then it converts the GTP into GDP and returns to the "off" position.
When mutated, KRAS can act as an oncogene, causing normal cells to become cancerous. The mutations can shift the KRAS protein into the "on" position all the time. KRAS mutations are common in pancreatic, lung and colorectal cancers. These KRAS mutations are said to be somatic, because instead of coming from a parent and being present in every cell (hereditary), they are acquired during the course of a person's life and are found only in cells that become cancerous.
Tumor mutation profiling performed clinically at the MGH Cancer Center has identified KRAS mutations across a broad-spectrum of cancer types. The highest incidence of KRAS mutations have been found in pancreatic cancer (70%), colon cancer (30%), lung cancer (25%), cholangiocarcinoma (15-20%), acute myeloid leukemia (15-20%) and endometrial cancer (15-20%). Across the other major tumor types, KRAS mutations have been found in less than 10% of cases that have been tested.