BICD 100 FALL 2017 WRITING ASSIGNMENT #4 INSTRUCTIONS

For this writing assignment you are being asked to write an argument (claim, evidence,

proposed explanation) regarding Figure 2 and Figure 3 (pasted below with some background

info) from Alexandrov et al. 2016. Mutational signatures associated with tobacco smoking in human cancer. Science 354(6312), 051417.

http://science.sciencemag.org/content/354/6312/618

Your argument should address the following research question:

Is there a relationship between tobacco smoking and the types and frequencies of

mutations and methylation changes in cancers of tobacco smokers?

– Decide on an appropriate claim given the data and the context of the paper.

– Describe the evidence in the assigned figures that supports your claim.

– Provide an explanation for these results (connect the genetics/biology to the results)

All components will be evaluated for correctness and completeness (see argument grading

rubric).

 If you use information from the papers listed above/below (or any others you find) be

sure to cite appropriately.

A second paper (Helleday et al., 2014) has also been posted on TritonEd as additional

background material that you may find useful for understanding mutational signatures.

Helleday, T., Eshtad, S., & Nik-Zainal, S. (2014). Mechanisms underlying mutational signatures in human cancers. Nature Reviews Genetics, 15(9), 585–598.

Maximum words: 450

Submission instructions

Submit your writing to Turnitin no later than Sunday Dec 10, 11:59pm.

This writing assignment is only due on Turnitin (via TritonEd) by Sunday Dec 10, 11:59pm.

BICD 100 FALL 2017 WRITING ASSIGNMENT #4 INSTRUCTIONS

Background information from Alexandrov et al. 2016 (you may find additional relevant

information in the paper):

“Tobacco smoking has been associated with at least 17 types of human cancer (Table 1) and claims the lives of more than 6 million people every year (1–4). Tobacco smoke is a complex

mixture of chemicals, among which at least 60 are carcinogens (5). Many of these are thought

to cause cancer by inducing DNA damage that, if mis-replicated, leads to an increased burden

of somatic mutations and, hence, an elevated chance of acquiring driver mutations in cancer

genes. Such damage often occurs in the form of covalent bonding of metabolically activated

reactive species of the carcinogen to DNA bases, termed DNA adducts (6). Tissues directly

exposed to tobacco smoke (e.g., lung), as well as some tissues not directly exposed (e.g.,

bladder), show elevated levels of DNA adducts in smokers and, thus, evidence of exposure to

carcinogenic components of tobacco smoke (7, 8). Each biological process causing mutations in

somatic cells leaves a mutational signature (9). ”

“In this study, we examined 5243 cancer genome sequences (4633 exomes and 610 whole

genomes) of cancer classes for which smoking increases risk, with the goal of identifying

mutational signatures and methylation changes associated with tobacco smoking (table S1). Of

the samples we studied, 2490 were reported to be from tobacco smokers and 1063 from never-

smokers (Table 1). Thus, we were able to investigate the mutational consequences of smoking

by comparing somatic mutations and methylation in smokers versus non-smokers for lung,

larynx, pharynx, oral cavity, esophageal, bladder, liver, cervical, kidney, and pancreatic cancers”

“We then extracted mutational signatures, estimated the contributions of each signature to each cancer, and compared the numbers of mutations attributable to each signature in smokers and

non-smokers.” (Figure 2).

“Differential methylation of the DNA of normal cells of smokers compared to nonsmokers has

been reported (28). Using data from methylation arrays, each containing ~470,000 of the ~28

million CpG sites in the human genome, we evaluated whether differences in methylation are

found in cancers.” (Figure 3).

Note: benzo[a]pyrene is a tobacco smoke carcinogen.

Please read the figure captions associated with each figure carefully.

BICD 100 FALL 2017 WRITING ASSIGNMENT #4 INSTRUCTIONS

BICD 100 FALL 2017 WRITING ASSIGNMENT #4 INSTRUCTIONS