Wednesday, October 24, 2012

Can we turn cancer into a more manageable disease, like Diabetes, in our lifetime? Hopeful New Genetic Targets from Multi-Platform High-Throughput Sequencing: Individualized Medicine, Here We Come!

This slide was taken from: Sandhu et al., Microarray-Based Gene Expression Profiling For Molecular Classification of Breast Cancer and Identification of New Targets for Therapy. These are hematoxylin and eosin stained breast cancer sections from different patients displaying distinct types of  breast cancer. First pay attention to the histology without the brown stain on the far left. Try to notice differences between Luminal A, Luminal B, Her2, and Basal-like types. Now look at the rest of the figure. Note that the blue is marking the nuclei of individual cells and the brown is marking a specific cellular target: on the second column to the left the antibody is against the estrogen receptor, the next column the antibody is to the progesterone receptor, the next column the antibody is against the HER2 receptor tyrosine kinase. In the article, you will see that these three markers have been the main ones used to distinguish breast cancer types and determine a therapeutic approach. Also, please be careful, because this slide represents an extremely general view of these breast cancers. Imagine, that each subtype has enormous histological heterogeneity, as well as mRNA heterogeneity which you will read about in the articles. For example, Her2 might be expressed in certain luminal types, and might even be devoid in some "Her-2 types". Hmmm...Fathom that!
Instructions for week of October 29-November 2nd: 
We are going to take a skip to Cancer Genetics. So after finishing chapter 10 on Chromosome Structure, please read: Chapter 22  (focus on section 22.4, The Genetic Basis of Cancer). You should also read sections 1 & 2 in Chapter 21 (focus on the DNA Microarray technique, The Proteome, and Protein Microarrays) and revisit Chapter 20 pages 559-565 on Next Generation Sequencing.

Instructions for Discussion on November 2nd:
In the beginning of this month, a landmark paper was published in Nature for Breast Cancer Research. (Thanks Mo for passing it to me) A global consortium of cancer biologists worked together using six high throughput platforms with a common goal: to identify novel targets in breast cancer and to attempt to better define the four emerging breast cancer subtypes. I have posted this article (but not the supplements, please go to Nature directly for those if you have time) and a review article on breast cancer subtypes on Black Board (with link below).

Instructions for the blog:
Please remark on one interesting aspect of breast cancer that you have learned for the first time from reading the Nature article and/or the review. For class: please identify one finding in the paper that seems to be novel for breast cancer research. It may be a missense mutation specific to one of the breast cancer subtypes, or a technique that was used in their study in a very different/comprehensive manner, or whatever you find interesting. Be prepared to share with the class your interesting finding.

For Nature article, Click Here: Breast Cancer Molecular Portraits_Nature Article
For Breast Cancer Review Article (a softer introduction to the topic), Click Here: Review article on Breast Cancer Subtype Array Analysis_Lab Medicine Journal