Discrepancy in Adenoma Carcinoma Colon Cancer Sequence

wanderluste

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    I don' t know if I'm just being daft, but, I feel like there's a discrepancy btwn FA+Pathoma and UWORLD. Pathoma and FA both say that APC mutation increases your risk for the adenoma (polyp), and then RAS mutation gives u the polyp and then p53 mutation makes it cancer.

    but i've had 2 Uworld questions already and one was where there was a pic of a polyp and it said what gene was mutated..and it was APC. and in the description for the answer it said that APC gives u a small polyp, RAS makes it larger, and then p53 mutation makes it carcinoma. The following question also had the same thing written.

    Am i just interpreting the things wrong? idk if any of you came across this when u were studying..

    Thanks guys!
     

    Goober11

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      I noticed this as well. Wouldn't UW's definition make the most sense though? After all JUST having a mutated APC gene in Familial Polyposis, that earns you 1000s of little POLYPS. Not just the propensity to make a polyp after a KRAS mutation. Am I making sense?

      Eventually one or a few of those little polyps acquire more mutations (KRAS, p53) and become a real problem.
       

      calvnandhobbs68

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        I noticed this as well. Wouldn't UW's definition make the most sense though? After all JUST having a mutated APC gene in Familial Polyposis, that earns you 1000s of little POLYPS. Not just the propensity to make a polyp after a KRAS mutation. Am I making sense?

        Eventually one or a few of those little polyps acquire more mutations (KRAS, p53) and become a real problem.

        Right that's why I've been going with the UWorld layout. I just annotated it into FA but I got it wrong in the first place because of Pathoma :thumbdown:

        Edit: Haha okay so I just did another question (Q 431 if anyone else has already done it) that seems to show 1) APC inactivation just causing a hyperproliferative epithelium 2) K-RAS activation occurring before adenoma formation and 3) COX-2 overexpression occurring before K-RAS activation. wtf is going on here.
         
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        Charles_Carmichael

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          Carcinogenesis, unfortunately, isn't as simple as the layout of the adenoma-carcinoma sequence in books makes it out to be. APC tends to be one of the earliest hits, but there's really no specific order of mutations beyond that. Mutations, such as k-ras, etc, are important events, but there's nothing that dictates that a k-ras mutation will be the first one after loss of APC or anything like that.

          I would know what the important mutations are and what they tend to cause (ex. hyperplasia, adenoma, etc), but I wouldn't commit one particular sequence of hits to memory, since that's not really how cancer works. It's an insanely complicated, multi-step process where the order of mutations is inconsistent. Make sense?

          Hope that helps.
           

          Phloston

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            APC gives u a small polyp, RAS makes it larger, and then p53 mutation makes it carcinoma.

            That's right. That's exactly how you need to memorize it for the Step1.

            -----------

            Bear in mind that on the real deal, if they ask you a question on this, it's going to be absurdly straightforward. They'll show you the sequence diagram THE SAME AS IT'S SHOWN IN FA, but one of the boxes/labels will be missing, and you'll have to identify it.

            If they say a patient had a small polyp per colonoscopy --> APC.

            If they say a pt had a small polyp that wasn't excised but then went back a year later and had a larger polyp --> RAS.

            If they show you a histological image without BM penetration --> APC or RAS.

            If they mention/show any form of invasion --> p53.

            I've never actually seen DCC show up in a practice question (even though it's in FA), but it theoretically goes hand in hand with p53. If they mentioned a DCC mutation, I'd go with basement membrane penetration.
             

            Goober11

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              That's right. That's exactly how you need to memorize it for the Step1.

              -----------

              Bear in mind that on the real deal, if they ask you a question on this, it's going to be absurdly straightforward. They'll show you the sequence diagram THE SAME AS IT'S SHOWN IN FA, but one of the boxes/labels will be missing, and you'll have to identify it.

              If they say a patient had a small polyp per colonoscopy --> APC.

              If they say a pt had a small polyp that wasn't excised but then went back a year later and had a larger polyp --> RAS.

              If they show you a histological image without BM penetration --> APC or RAS.

              If they mention/show any form of invasion --> p53.

              I've never actually seen DCC show up in a practice question (even though it's in FA), but it theoretically goes hand in hand with p53. If they mentioned a DCC mutation, I'd go with basement membrane penetration.

              This is very clear, thank you.
               

              wanderluste

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                That's right. That's exactly how you need to memorize it for the Step1.

                -----------

                Bear in mind that on the real deal, if they ask you a question on this, it's going to be absurdly straightforward. They'll show you the sequence diagram THE SAME AS IT'S SHOWN IN FA, but one of the boxes/labels will be missing, and you'll have to identify it.

                If they say a patient had a small polyp per colonoscopy --> APC.

                If they say a pt had a small polyp that wasn't excised but then went back a year later and had a larger polyp --> RAS.

                If they show you a histological image without BM penetration --> APC or RAS.

                If they mention/show any form of invasion --> p53.

                I've never actually seen DCC show up in a practice question (even though it's in FA), but it theoretically goes hand in hand with p53. If they mentioned a DCC mutation, I'd go with basement membrane penetration.

                THANK YOU. You make things really clear! I want to get to your point in knowledge base, good sir! I was just about to ask you the diff btwn mesenteric ischemia and ischemic colitis....but i searched this forum first...and sure enough, you had provided an answer to that person's same question as well!! You are awesome!
                 
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                Jamiu22

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                  You yourself said that APC deletion is a type of DCC though.. What am I missing?

                  No APC is not a type of DCC; DCC, although called Deletion in Colon Cancer is actually a specific gene that codes for a DCC protein.. while APC is another gene that's more often associated with cancer predisposition.

                  But as in all cancers, the progression of a defect to cancer typically involves multisteps and other mutation for the neoplastic cells to grow uncontrollable and then invade. The multisteps required are typical multistep required in colon cancer are APC (typically congenital as heterozygous) -> RAS (acquired) -> P53 (acquired)

                  Check out Pg359 FA2012; Hope this helps...
                   

                  Myxedema

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                    okay i think i figured out what you guys are saying, based on UW question 428 [465277]

                    1. APC loss -> adenomatous polyp
                    2. K-ras mutation -> increase in size of polyp
                    3. DCC -> polyp transforms to adenoma
                    4. p53 loss -> adenoma transforms to carcinoma

                    Polyps are already adenomas.

                    F1.medium.gif
                     

                    CDI

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                      UW also mentions that colorectal carcinoma associated with ulcerative colitis is more likely due to an early p53 mutation and late APC mutation, opposite that of sporadic colorectal carcinoma

                      This is the exact concept I got asked on my real exam. I botched it due to recall error. Know this difference (between ulc col crc & sporadic crc) and also HNPCC & FAP. Should be easy points if you take 5 mins to just memorize it.
                       
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