Tuesday, February 02, 2016 |
Written by Prashanth Suravajhala. Published with permission.
Majority of the eukaryotic genomes do not code for proteins, i.e. there are regions that might originate within the organisms or tissues without coding potential. If they do not code, it was earlier supposed to be of disinterest as they wouldn’t be associated with any disease. However, the last decade has seen advances in the field with certain (non-coding) RNA molecules transcribed; regulate expression of genes and further known to affect the transcription and cell cycle of diseased organism. A class of such non-coding RNAs identified during the last decade is long non-coding RNAs (lncRNA) that are known to play a role in diseases particularly cancer. What ails breast cancer in terms of lncRNAs? Are there such molecules associated with breast cancer? If so, can these be used as prognostic or diagnostic markers? Can these candidate markers be used for prevention or treatment of breast cancers?
Yes, says the research paradigm! Studies have demonstrated that the changes in lncRNA expression in tissues have been associated with metastasis, tumorigenesis of cancers. If such tissue specific expression patterns are found, a clinically beneficial possible biomarker could be made available for treatment (See Figure 1 below). Such expression levels are examined largely by RNA-Seq (transcriptomic) studies which further shed light on their biological functions even as they further provide information on discovering potential therapeutic targets. Having said this, there is a remarkable scope to understand breast cancer specific lncRNAs towards:
- Identification of markers to distinguish normal from tumor cells.
- Understanding etiology, pathology stages and ascertaining new therapeutic targets.
- Applying functional proteomic strategies for sub-tissues of potential clinical interest.
Figure 1 (a): The lncRNAs are synthesized, form complexes (primary miRNAs etc.) from various intranuclear bodies as a part of transcriptional events. They are usually more than 200 and maximum of 10k bases in length. (b) Outside nucleus, in the cytoplasm they interact with various proteins by the advent of RNA-binding complexes. If lncRNA binds to a known breast cancer diseased gene (for example, BRCA1), then such candidates can be further validated for marker studies.
Select references of interest
- Liu Y, Sharma S, Watabe K. Roles of lncRNA in breast cancer. Front Biosci (Schol Ed). 2015 Jun 1;7:94-108. Review. PubMed PMID: 25961689.
- Wang G, Liu C, Deng S, Zhao Q, Li T, Qiao S, Shen L, Zhang Y, Lü J, Meng L, Liang C, Yu Z. Long noncoding RNAs in regulation of human breast cancer. Brief Funct Genomics. 2015 Nov 18. pii: elv049. PubMed PMID: 26582840.
- Vikram R, Ramachandran R, Abdul KS. Functional significance of long non-coding RNAs in breast cancer. Breast Cancer. 2014 Sep;21(5):515-21. doi: 10.1007/s12282-014-0554-y. Epub 2014 Jul 20. Review. PubMed PMID: 25038622.
Thursday, January 21, 2016 |
MyID Breast Cancer is honored to sponsor a post by Prashanth Suravajhala, a biologist and bioinformatician who built and released a database in 2007 contains all human hypothetical proteins.
Please tell us why you are involved in the Breast Cancer community?
I am a Postdoctoral bioinformatics researcher engaged in research on identifying the known unknown regions or variants associated with diseases. We have indeed worked on a couple of well known cancers like hepatic carcinoma, lung etc., but have a great interest in finding such variants and regulatory regions associated with BRCA genes. On the latter, no.
Why are you involved in spreading information about Breast Cancer on social media platforms?
I am socio/tech-savvy, love to share and beleive in an adage that "One Who shares, wins"
What interesting research, tips, recipes, or story can you share with our Breast Cancer Community?
I'd be glad to contribute on updates and developments on Systems Biology of BRCA and the regulatory effects the disease has seen in the recent past. To start with my first topic would be on "Long noncoding RNAs in Breast Cancer and their implications." I can send this ASAP.
Finally, what link would you like to share with the community?
Prash was also the winner of the PLOS Synthetic Biology T-shirt design contest which displays his incredible work with hypothetical proteins.
Tuesday, September 29, 2015 |
For the past 10 years, doctors have used a genetic test to decide which patients may be able to skip chemotherapy after surgery for breast cancer.
Now a study confirms that this test, called Oncotype DX, works well for a small group of patients. But a longer, follow-up study is needed to draw conclusions for a fuller range of patients with riskier tumors.
Oncotype DX analyzes 21 genes in the tumor to estimate a woman's risk of the cancer coming back after surgery.
For patients who fell into the test's low-risk category, 99 percent didn't develop metastatic breast cancer five years after surgery, even though they didn't have chemotherapy. The overall survival rate among this group was 98 percent, doctors reported Monday in the New England Journal of Medicine
"This is really great news for the patients we're treating" says Dr. Sharon Giordano, an oncologist at MD Anderson Cancer Center in Houston, who wasn't involved in the study.
Oncotype DX is recommended by the American Society of Clinical Oncology and is considered the standard of care for a particular type of breast cancer, Giordano says.
Each year, about 230,000 Americans are diagnosed with breast cancer. About 100,000 qualify for the Oncotype DX, and 16,000 fall into the low-risk category. The test costs about $4,000 and is covered by most insurers.
"It's important that the test was validated, but also how low the risk of recurrence actually was for this subset of patients," she says. "Chemotherapy is more likely to harm these patients than to help them."
In the study, doctors around the country, gave the Oncotype DX test to more than 10,000 women diagnosed with a common form of breast cancer that responds to anti-hormone treatments. About 16 percent of the women scored low on the test and thus, received only anti-hormone therapy, no chemotherapy.
Five years later, this group of women were more likely to develop another type of cancer — or die of something other than cancer — than they were to have their first tumors return somewhere else in their bodies.
"This is very reassuring that the guidelines we've been following are right," says Dr. Daniel Hayes, who co-directs the Breast Oncology Program at the University of Michigan and contributed to the current study. "It's one more step forward to personalizing how we treat patients."
But, for a large percentage of patients, the Oncotype DX test is still ambiguous, Hayes says. Nearly 70 percent of the patients in the study scored in the mid-range of the test and were considered a moderate risk for a relapse.
Hayes and his colleagues are now testing to see which of these patients benefit from chemotherapy. The results of that trial are due out in a few years.
Read more at NPR