Tumor Suppressor Genes: VHL, WT, NF, BRCA, DCC – Carcinogenesis

by Carlo Raj, MD

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    00:01 These tables are huge upcoming. I will give you stories for each one of this. My topic is tumor suppressor gene.

    00:07 You thought perhaps that p53 and Rb was sufficient. I know you did'nt think that. But those are good examples to kick start our discussion of tumor suppressor gene. So what if you had a mutation in which you lose your tumor suppressor.

    00:21 Obviously now can we say that you are going to develop cancer. Okay. Now, let's take a look at other important tumor suppressor genes that you will be responsible for and what kind of cancer does it develop. Von Hippel-Lindau disease. Normally, this is a tumor suppressor gene. Normally, Von Hippel-Lindau which we will talk about later further controls what's known as hypoxic inducible factor 1-alpha. HIF-1-alpha. That is a factor that controls, VEGF. Am I giving you too much detail.

    00:53 Have you met me. Everything that I tell you is imperative to know for your boards. So you can get your 250, 260, 270.

    01:02 There is no ceiling as far as what you can score. Just every once in a while take a deep breath and come back. Von Hippel-Lindau controls your hypoxic inducible factor 1-alpha. This controls VEGF. That controls angiogenesis. Go back to the basics.

    01:24 Cancer, neoplasia, increased proliferation. How much angiogenesis do you require? Forever. You want as much angiogenesis as possible.

    01:35 So that you can do what? Supply blood to your cells, the cancer cells, so they can breath just like you and I.

    01:43 What's the name of that factor? VEGF. Vascular endothelial growth factor. So if VHL has been lost, you are going to have increased VEGF activity and the type of cancer that you definitely want to know it's association with is renal cell carcinoma. We'll talk further if things called hemangioblastomas and those hemangioblastomas will be located in the cerebellum or maybe up in the retina. Now we're going to childhood renal cancer. Before we move on, one quick little note.

    02:14 With VHL, that is not the only cause of RCC, you are aware of that. You can have an older patient that is smoking and they would then perhaps 10% of the time present with hematuria and flank pain and also weight loss, that has nothing to do with VHL. Okay.

    02:31 This is a genetic cause of RCC and then you can have environmental factors. So if RCC is to an adult, then what kind of renal cancer is equivalent to a child. Welcome to Wilms' tumor. Now those of you that have memorised the acronym WAGR and nowadays because complements of DSM-V, we can no longer say mental retardation so we have to say intelectual disability. Maybe you change the acronym WAGR to WAGI. Whatever it may be. W in WAGI, Wilms' tumor. A, aniridia. G, genital abnormalities, and intelectual disability.

    03:16 This is WT-1. Make sure from embryology, you know quite well about WAGR, that's probably what you have learned it as.

    03:25 Wilms' tumor, WT-1. WT-2 is never associated with WAGR. Students get that confused and they choose the wrong WT. This is a simple question.

    03:39 You have a childhood renal cancer and if the patient is walking like this and I can't walk too much here but if it's half the body that's bigger than the other half literally. It's called hemi- hypertrophy. Also the tongue, wide. Macroglossia.

    04:01 Organs, wide. Visceromegaly. Everything in your body is wide along with hemihypertrophy. This is called Beckwith?Wiedemann or maybe you might want to pronounce it as Beckwith-Widemann. Widemann. Everything is wide. Half the body is wide. This is WT-2.

    04:26 There is huge difference between WT-1 and it's presentation of Wilms' tumor, aniridia. Could you imagine not having an iris.

    04:35 It's really peculiar. Genital abnormality and R stands for mental retardation or intelectual disability. WT-2 is also renal cell carcinoma in a child associated with Beckwith-Widemann. Then we have NF-1. NF-1 is neurofibromatosis type 1 and the type of cancer that neurofibromatosis type 1 gives rise to is neurofibroma. Often times students get this confused with NF-2.

    05:06 Well do this for me. How many ears you have? One, two. Eight cranial nerves has to supply both. Where is your cranial nerve VII? At the angle between the cerebellum and a pontine. Picturing that. Cerebellopontine. The angle there, if they are to develop cancers with NF-2. Neurofibromatosis type 2. This is called what? Acoustic neuroma. Another name for this is Schwannoma. So from henceforth if you ever got confused with NF-1 and NF-2, hopefully no more. NF-2 could also be associated with meningiomas. BRCA-1 BRCA-2 I will put this together for you. Both of this associated with breast and ovarian cancer. That's all that I wish to say about this two. Then you have DCC. It is associated with colon cancer. Also do not forget with colorectal cancer you can have receptor tyrosine kinases that is important for pharmacology. You have heard of the drug siltuximab. If you have'nt look it up.

    06:11 Siltuximab. Guaranteed you will be given on siltuximab. DCC is positive, CEA might be positive, p53 might be knocked out and RAS might also be knocked out. Welcome to colorectal cancer, multifactorial.

    About the Lecture

    The lecture Tumor Suppressor Genes: VHL, WT, NF, BRCA, DCC – Carcinogenesis by Carlo Raj, MD is from the course Cellular Pathology: Basic Principles.

    Included Quiz Questions

    1. Von-Hippel Lindau disease
    2. Wilms' tumor
    3. Colon cancer
    4. FAP
    5. Breast cancer
    1. WT-1
    2. WT-2
    3. VHL
    4. DCC
    5. NF-1
    1. Neurofibromatosis type II- NF-2- acoustic neuromas
    2. Neurofibromatosis type I- NF-1- schwannomas
    3. Neurofibromatosis type I- NF-1- meningiomas
    4. Neurofibromatosis type II- NF-1- neurofibromas
    5. Neurofibromatosis type II- NF-2- neurofibromas
    1. BRCA-1
    2. BRCA-2
    3. DCC
    4. VHL
    5. NF-2

    Author of lecture Tumor Suppressor Genes: VHL, WT, NF, BRCA, DCC – Carcinogenesis

     Carlo Raj, MD

    Carlo Raj, MD

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