Antonio and
I started our search on cancer by looking at an issue that people could relate
to. Understanding that we are in college, we looked to the affects alcohol has
on cancer. What we first found is that alcohol is directly related to a set of
cancers called HNSCC or Head and Neck Cancer. These cancers have to do with the
oral, nasal, pharynx and larynx areas.
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| Source: Reference 3 |
Compared to other cancers, HNSCC has the sixth largest number of
incidences in the world with about 600,000 new occurrences every year worldwide.
It also can be quite devastating for patients who are in the late stages of
this cancer because the 5-year survival rate after treatment is only about
40-50 percent.
Based off of this, we further researched into HNSCC and found a gene
mutation that caught our attention. This gene is known as NOTCH1. Mutations in NOTCH1
can be found in about 15% of HNSCC cases making it the 2nd most
mutated gene in this type of cancer. NOTCH1
encodes for a receptor protein that spans through the membrane. When activated,
the cytoplasmic end of this protein gets cleaved and acts a transcription factor
that increases the expression of genes that help with cell differentiation.
With this basic knowledge, it is easy to understand why mutations in this gene
can cause cancer.
In an Exome Sequencing Study of HNSCC, published on Sciencemag.org in July 2011,
a group of researchers used Affymetrix
SNP6.0 microarrays (which depict genetic abnormalities) to compare 42 normal
and tumor samples pairs. With this, they came up with this figure that showed a
general map of NOTCH1 mutations in
different types of tumors.
 |
| Source: Reference 1 |
In simple terms, this image shows NOTCH1
mutations for three different sets of tumors with set C displaying the
mutations observed for HNSCC. This image essentially gives at least two
conclusions, one being that HNSCC can act in different manners in different
types of cancer, and two being that HNSCC’s have a significantly higher amount
of mutations in the NOTCH1 gene
compared to the other two sets of cancers that were analyzed. Further looking
at these mutations and understanding previous literature about the NOTCH1 gene in different types of
cancers, this study concluded that NOTCH1
does in fact act differently in different types of cancers. For example, in T-cell Leukemia, this gene acts as an
oncogene. However, in HNSCC’s this gene acts as a tumor-suppressing gene. Throughout
our research, Antonio and I hope to further understand why and how this happens
and hopefully look at possible treatments for both threats that mutated NOTCH1 presents.
Sources:
Agrawal, N., Y.
Wu, C. R. Pickering, C. Bettegowda, L. D. Wood, K. Chang, R. J. Li, C. Fakhry,
T.-X. Xie, J. Zhang, J. Wang, N. Zhang, V. E. Velculescu, A. K. El-Naggar, S.
A. Jasser, J. N. Weinstein, R. H. Hruban, J. N. Myers, W. H. Westra, W. M.
Koch, J. A. Califano, R. A. Gibbs, D. Sidransky, N. Papadopoulos, B.
Vogelstein, D. A. Wheeler, K. W. Kinzler, D. M. Muzny, J. A. Drummond, L.
Trevino, and M. J. Frederick. "Exome Sequencing of Head and Neck Squamous
Cell Carcinoma Reveals Inactivating Mutations in NOTCH1." Science
333.6046 (2011): 1154-1157. http://www.sciencemag.org/content/333/6046/1154.full#xref-fn-1-1.
Web. 12 Apr. 2014.
Brakenhoff, R.
H.. "Another NOTCH for Cancer." Science 333.6046 (2011): 1102-1103.
http://www.sciencemag.org/content/333/6046/1102.full. Web. 10 Apr. 2014.
M., Grønbaek,
Becker U., Johansen D., Tønnesen H., Jensen G., and Sørensen T..
"Population based cohort study of the association between alcohol intake
and cancer of the upper digestive tract.." National Center for
Biotechnology Information. U.S. National Library of Medicine, 26 Sept.
1998. Web. 21 Apr. 2014. <http://www.ncbi.nlm.nih.gov/pubmed/97
