Day 5/10 | TEN ON TEN 4.0 | #inicet #fmge #neetpg

追加: 2026-05-16

[00:00:01]Hi everyone, welcome to day five of the 10 on 10 series. Today we have your favorite topic that is genetic mutations, few chromosome numbers, match the following, a lot coming your way. 10 questions, let's get going. The first one over here is asking you about sickle cell anemia. Usually if it comes as a clinical history, it will be a 14-year-old boy with bone pains. That's their favorite history because sickle cells tend to cause occlusion, vaso-occlusion, and hence bone pain.

[00:00:25]They are saying glutamic acid will go, valine will welcome, you know that and that will happen at the beta globin chain, but what kind of a mutation is it? Since it's happening at one point, it is a point mutation. And because of this mutation, the original adult hemoglobin which was supposed to form is now replaced and will be changed into sickled hemoglobin. So the sense has changed, right? The hemoglobin type has changed. That is why it is a type of a missense point mutation. If on the other hand, they because of this mutation nothing would have changed at all, the patient would have still continued to have adult hemoglobin. I would have said that this mutation has gone unnoticed or it has gone silenced. The third option is that because of a point mutation, maybe the hemoglobin production all together stops and that will be a nonsense mutation. For example, in cases of thalassemia, it is not that one hemoglobin is changing into another. It is actually that hemoglobin production together all together stops and that becomes a nonsense mutation. Let's move on to question two. Looks difficult, but if you remember the story from rapid revision and that stories are what remain with you for a longer time.

[00:01:30]They're asking you which of the following statement regarding RB gene or protein is correct with its role to the cell cycle. If you remember the story and first you get your answer and then move on to marking it, it will be easier for all of us. We all know that the RB gene is normally in a very healthy, happy relationship with E2F. Everything is happy and good till the time a third person enters into this relationship called phosphate. As soon as phosphate comes, RB gene gets phosphorylated, goes away with phosphorus. And that is why who's left alone? E2F is left alone and you know if it's left alone, it has been ditched, it is going to come back and its comeback is that it will go and start the cell cycle at the very first phase and that is the G1 S phase. So the cell cycle is now going to continue. So can I say indirectly that till the time RB gene did not have phosphorus like in its normal state, it was bound to E2F and till the time it was bound to E2F, they were so busy in each other, they were not activating the cell cycle. This means they were preventing the cell cycle from being gone, going. And that's the best answer. So as I said, you are supposed to first figure out your answer, figure out what you know in your concepts and then apply that because all the others as you keep reading, they're just going to add on to the confusion.

[00:02:43]Tells me normal RB gene is hypophosphorylated.

[00:02:46]When it will get hyperphosphorylated, that is when E2F is left alone and that is when E2F will go and activate the cell cycle. Moving on to question number three, amplification of N-myc gene is a prognostic indicator and for N classical question that is going to be neuroblastoma. I'm not discussing the others because that's exactly question number four where they've asked you. I have a couple of match the followings coming, so all the other options will be discussed, but before that, they've asked you follicular lymphoma. I'll put a big smiley in front of it because with regard to non-Hodgkin's lymphoma, it's got the best prognosis. It is teenagers friendly, so 14-18 translocation and they are saying that is going to result in over-expression of BCL2.

[00:03:27]What is the mechanism for this? If you remember BCL, anything with the alphabet L was lowering apoptosis or was anti-apoptotic. I'm saying that BCL2 is suddenly going to be expressed too much.

[00:03:40]This means all these cancer cells are cancerous because they are lowering apoptosis. They are escaping apoptosis and that is going to be their mechanism of action and hence they are cancer because they're not getting killed. They are escaping apoptosis, escaping cell death and hence we call them cancer cells. Let's move on to the next question. Here start your match the following. Right now you did BCL2, what would you want to match it with?

[00:04:02]Follicular lymphoma translocation 14-18.

[00:04:05]Then you have KRAS. KRAS I'm sure reminds you of the couple tumors and in the couple tumors you have colon, pancreas, and lung. What do I have over here? I have pancreatic adenocarcinoma mentioned which I can match. Then who will not be knowing HER2 gene for breast cancer, even for ovarian cancer? Then we have RET and for RET we have always studied RET 10 med men. So RET is the name of the gene, chromosome number 10, which is the cancer with which it is associated, medullary carcinoma thyroid.

[00:04:34]And what are the two syndromes with which this can be associated? MEN2A and MEN2B. Not to forget for medullary carcinoma thyroid, the tumor marker is calcitonin and when this converts to amyloid, it is going to be A cal. Moving on to question six, another match the following. So we have translocation 15-17, the one that is associated with AML M3, acute promyelocytic leukemia, the only leukemia which can cause DIC and death in patients. The next one is translocation 11-22, that is Ewing's sarcoma. We had studied E for 11, S can be flipped into a two, so translocation 11-22. And when I talk about the genes, EWS is the first gene that we have and wings, E wing, wing help you fly, so fly one fusion is what is noted. Now let's come to translocation X and 18. X is 18 and that is going to be synovial sarcoma. When do we commit sins? When we become adults. When we children don't commit sins, we commit sins when we become adult and the adult age is of course 18 because usually options also have X and 17 etc. So X and 18 translocation is when we'll commit sins and that is synovial sarcoma. What am I left with? Translocation 1-2-2-1 with B ALL, good prognosis because anything with the number three for ALL will be good. So any trisomy given with ALL, for example trisomy 4, 7, 10, it is good.

[00:05:58]Translocation 1-2-2-1 is also good like mentioned over here because both of them, 1 + 2 is 3, 2 + 1 is also 3, so anything coming to 3. But what is the most common genetic abnormality in ALL?

[00:06:10]That is going to be hyperdiploidy which means more than 2N. More than 2N will obviously mean what? 3N, right? And anything with three is again good for ALL.

[00:06:20]Moving on to another match the following. HPV, we have to get a question on HPV this exam. E6 and E7, E6 will go and deactivate P53 gene. E7 will go and deactivate RB gene, we know that.

[00:06:33]Then let's come to EBV and HTLV. HTLV causes all T cell leukemia lymphomas.

[00:06:38]How does it cause? It has a tax gene in it and that is how it causes the TTT things coming together. So what am I left with? Maybe you don't have to learn it, but what's option that's left is EBV makes a protein called LMP1 which goes and mimics the CD40 signaling pathway.

[00:06:54]Moving on to another match the following. Tumor suppressor genes and their numbers. Who can forget the policeman? It's present on chromosome 17p13 and if you continue from 13, then the governor or RB gene is present on 13q14.

[00:07:09]Then we have WT1. The way you write W, it reminds you of 11. So this is going to be 11p, it is the Wilms tumor. And APC, the one that causes familial adenomatous polyposis is present on chromosome 5q21.

[00:07:22]Now I come to two one-liners probably.

[00:07:25]Epigenetic silencing of tumor suppressor genes in cancer frequently involves the modifications of those ATCG nucleotides.

[00:07:33]The modification of CG islands or CpG islands. If they're talking about epigenetic silencing or muting, for muting I will always go with methylation. If you want to make a gene mute or you want to make a gene silent, you will be going with methylation. If you would have had to make it active, you would have gone for acetylation. So repeating, hypermethylation is what we are going to go ahead with for muting or silencing. Coming to the last question, they are asking you which molecule will get downregulated in EMT?

[00:08:05]You need to understand what is EMT. E for epithelial. Epithelial cells usually are round like the epithelium of the skin etc. And when they will convert to mesenchymal, mesenchymal are spindle. So I'm talking about epithelial mesenchymal transition that happens in cancer cells.

[00:08:21]Do you know all the epithelial cells, they all have a fevicol on their surface called E-cadherin? And when this will go downregulated, that is when they are changing into mesenchymal. So downregulation of which molecule is needed? E-cadherin. That is when the epithelial cells will change into mesenchymal. And why is that even being Why is that happening in cancers? Why are epithelial cells losing their E-cadherin? Why are they changing to mesenchymal? Because this will then help the cells to detach. And till the time the cancer will not detach, how will it spread to different parts of the body?

[00:08:54]So this EMT is actually going to help in spread and cancer metastasis. Do you know who regulates this EMT process?

[00:09:02]There are two genes which are known as snail and twist. Typical INICT type of questions. That finishes off the 10 questions of the day. A lot of pathology done today, that is why tomorrow when we meet in the 10 on 10 series, we have lots of questions, images or five MCQs, five spotters on culture media. So let's keep that for tomorrow and see you again very soon.