Finding pathway for “Small Cell Lung Cancer (SCLC)” and examining the structure of genes involved in the pathway.

Small cell cancer of the lung accounts for about a fourth of the 110,000 new cases of lung cancer that occur annually in the United States. It is clinically distinctive: usually metastases are already present at the time of discovery so that surgery is not used. In contrast to adeno- and squamous carcinoma, SCLC is sensitive to chemotherapy and radiotherapy[1]

Many scientists might be interested in studying the SCLC pathway and examining the genes of the pathway so that they can design a drug to combat the disease. The following steps can be followed to retrieve pathway and gene information regarding SCLC.

1. Go to www.kegg.com

[ KEGG (Kyoto Encyclopedia of Genes and Genomes) is a collection of online databases dealing with genomes, enzymatic pathways, and biological chemicals. The PATHWAY database records networks of molecular interactions in the cells, and variants of them specific to particular organisms] [2]

2.Click on “ KEGG Disease” on the KEGG homepage.

3. Under the Disease Classification category click “Human diseases”.

4. Next type in “small cell lung cancer” in the search field.

5. Then appears a list of Cancers of lung and pleura.Click on H00013 for small cell lung cancer.

6. On the page that appears you will get a list of categories describing the disease.

7. Click on hsa 05222 in the pathway category and on the page that appears click on has 05222 in the pathway map category.

8. You will get pathway for small cell lung cancer.

9. If you go back and scroll down you will find a list of genes involved in the pathway Let us suppose that we want to study the structure and function of RB1 gene of the pathway. For this purpose follow the following steps:

1. Click on 5925 for RB1.

2. You will get complete information for RB1, including accession numbers for this gene in different databases.

3. Click on accession number for UniProt in the other DBs category.

4. On the resulting page click FASTA to retrieve FASTA format of the protein product of RB1.

5. Now go to http://www.ncbi.nlm.nih.gov/blast and click on “protein blast”. Paste the FASTA sequence for protein which you obtained for the protein from UniProt , select “protein databank” as the database and click on”BLAST”.

6. You will get a page that displays the graphical summary of hits and list of found sequences.

7. Go to the list of sequences and select the topmost PDB sequence ,which in this case is pdb| 1GH6 | B.

8. 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 then click on “structure”.

9. This leads us to MMDB summary for this structure.Click on 1GH6 and on the resulting page click on”view structure in Cn3D.You will get 3- dimensional structure of this protein.In this way the structrues for protein product of all genes involved in the pathway can be obtained.

Hence,we not only obtained pathway for small cell lung cancer but also viewed the structure of the gene (RB1) in the pathway.This can be done for all the genes involved in the pathway,and thus not only abnormality in the pathway can be studied but also the structures of genes in the pathway can be examined in detail .

References:

[1] http://www.ncbi.nlm.nih.gov/omim/

[2] http://www.wikipedia.org

Contributed by:Saba Khalid and Maleha Jamal