Breast cancer is a cancer that starts in the cells of the breast in women and men. Worldwide, breast cancer is the second most common type of cancer after lung cancer (10.4% of all cancer incidence, both sexes counted) and the fifth most common cause of cancer death. In 2005, breast cancer caused 502,000 deaths worldwide (7% of cancer deaths; almost 1% of all deaths)[1].

Knowing that protein structure is directly responsible for a protein's function, we are interested in viewing and understanding a protein's structure. We also know that many forms of cancer result due to mutations which modify the protein's structure. Naturally, to study the disease, we need to analyze the mutations, structural modifications caused by those mutations. In certain ways, the disease is the consequence this structural modification.

In this case study, you will learn how to detect a mutation and visualize the structure, given that this data is available in a bioinformatics database.

MMDB is a database that now provides us with a visualization tool known as “Cn3D”.This tool can be used in multiple ways,to retrieve sequences and structures but in this case study we will retrieve structure from a BLAST search.

1. Go to http://www.ncbi.nlm.nih.gov/omim/ and in the search field select OMIM and search for “breast cancer gene”.
2. You will get 631 results.
3. Click on +113705.
4. Read the topic “clinical features”(familial breast cancer).
   
   1. This shows that mutation in BRCA1 and BRCA2 causes breast cancer
   2. “The findings were interpreted as suggesting that breast cancer due to BRCA1 has a different natural history from BRCA2”[2]. We will use this concept and identify structural differences between BRCA1 and BRCA2 genes.
5. To find the accession number for the protein product of this gene ,go to www.expasy.org and in the search field type “breast cancer gene”.
6. You will get 86 results .click on “BRCA1_HUMAN”
7. The topmost line gives the accession number of BRCA-1 that is P38398.
8. Go to http://blast.ncbi.nlm.nih.gov and click on BLAST.
9. Click on “protein blast” an in the input box enter acc nos for BRCA-1 (P38398).
10. Select “protein databank” as the database and click on”BLAST”.
11. You will get a page that displays the graphical summary of hits and lsit of found sequences.



12. Go to the list of sequences and select the topmost PDB sequence ,which in this case is pdb| 1JNX | X.
13. This takes us to GENPept summary for this proteins sequence.on the right hand side of this page is the option of “Links”click it and the click on “structure”.
14. This leads us to MMDB summary for this structure.click on 1JNX and on the resulting page click on”view structure in Cn3D.



15. You will get two windows ,one will show the protein sequence and other will show the amino acid sequence of the protein.



16. Repeat steps 5-14 for BRCA-2 gene.
17. Thus,in the end you have the structure as well as sequence for BRCA-1 and BRCA-2 genes that cause breast cancer.
18. The two structures can now be analyzed .

References:

[1] www.wikipedia.org

Contributed by: Saba Khalid