Special report. Chronic Lymphocytic Leukemia (CLL) Genomic Biology 3020 April 20, 2006

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1 Special report Chronic Lymphocytic Leukemia (CLL) Genomic Biology 3020 April 20, 2006

2 Gene And Protein The gene that causes the mutation is CCND1 and the protein NP_ The mutation deals with the cell cycle which deals with cellular differentiation which results in the over expression and over production of the BCL 2 gene. The mutation occurs on chromosome 11q13

3 Gene mutations that cause CLL CCND1, PRAD1, BCL1 Cyclin D1 P2RX7, P2X7 Purinergic receptor P2X, ligand-gated gated ion channel, 7 ARL11, ARLTS1 ADP-riposylation factor-like 11 MIRN16-1, 1, MIR Micro RNA 16-1

4 Size of mrna and Protein NP_ is 295 aa This is the protein NM_ is 4304 bp This is the nucleotide The gene contains 5 exons which means there is only 4 introns

5 Conserved Domains of NP_ Protein binding domain functioning in cell- cycle and transcription control The cyclins consist of 8 classes of cell cycle regulators that regulate cyclin dependent kinases (CDKs)

6 Related Structure Diagram This is the related structure of 1G3N C which had an e value of 1e-27 Structure Of A P18(Ink4c)-Cdk6 Cdk6-K- Cyclin Ternary Complex No actual 3-D 3 structure yet available for CCND1

7 Chronic Lymphocytic Leukemia Chronic lymphocytic leukemia (CLL) is a condition characterized by an accumulation of abnormal white blood cells or lymphocytes in the blood and the bone marrow. These lymphocytes cannot perform their normal infection-fighting fighting functions and interfere with the production of other blood cells, leading to multiple complications including immune deficiency, bleeding, swollen lymph nodes and other conditions.

8 Mutations CLL is mainly caused by a mutation of CCND1 on chromosome 11q13 which causes the over expression and over replication of the BCL2 gene which is part of the B-B Lymphocytic apoptotic cycle pathway on chromosome 18q21.3 The result is the inability of apoptosis.

9 Mutations Two types of mutations have created two distinct groups of patients with CLL. The first mutation is a somatic mutation of the immunoglobulin genes of CLL These patients have a stable or slowly progressive disease and symptoms requiring late or no treatment

10 Mutations cont. The second type of mutation is the overall absence of the immunoglobulin gene mutation in CLL. The absence of this mutation created a group of patients with a highly progressive disease that required early and fast treatment.

11 More on Mutations The absence of immunoglobulin gene mutation is associated with the deletion of the ATM locus on chromosome 11q. The ATM gene deals with responding to DNA damage involved in DNA repair and cell cycle control The result is shortened life span of the patient

12 Hypothesis Due to the fact that CCND1 is involved in the cell cycle and the cellular regulation of cells, we hypothesize that our gene is involved in other types of cancers.

13 Proving the Hypothesis We researched the gene in ENTREZ Gene and found it to be involved breast cancer(brac1). Further research at the Cancer Genome Anatomy Project (CGAP) provided a list of cancers Cyclin D1 (CCND1) is associated with. Some include esophogeal,, colon, parathyroid adenomas (thyroid, stomach, etc), and numerous other cancers.

14 CGAP cont The cdna libraries at the CGAP provided the different types of cancers, location, tissue types etc. It is easy to see the reason to the numerous types of cancer. The fact that CCND1 is involved in the cell cycle and cellular regulation, a mutation in this gene will likely result in the person having cancer if not several types.

15 Proved Hypothesis If CCND1 is involved in this many types of cancers due to its mutation in the cellular cycle, can it be assumed that CCND1 is an oncogene? Hinds, Dowdy, Eaton, Arnorld,, and Weinberg proved the gene contributed to cellular transformation by complementing a defective E1A oncogene.. CCND1 is therefore considered an oncogene.

16 Works Cited NCBI- CGAP- PUBMED- Function of a human cyclin gene as an oncogene query.fcgi?cmd=retrieve&db=pubme d&dopt=abstract&list_uids=

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