Homework
Homework
Homework
Please read and follow these instructions carefully. Make sure you
understand what you have to do before attempting to complete this
assignment.
The purpose of this assignment is to get you to synthesise information about cancer and epigenetics gleaned
from the lecture videos, and the following scientific review paper and article in the popular press:
Part of being a good scientist is to read widely, attend talks, understand the key concepts and in turn
communicate these concepts to others. During this writing assignment you will get a taste of what this
experience is like.
The writing assignment is broken down into four (4) main questions. Each question includes specific details
to help you identify the critical points you should be making and ensure you meet the grading criteria. Good
scientific writing is clear and concise, so there is a word limit for each question. Your answers should be
written in prose form and not bullet points or lists.
You will need to complete all four parts and enter your answers in the ‘My submission’ section (see
above tab).
Review criteriamenos
You will need to review five (5) of your peers' work as part of this assignment after you have made your own
submission.
Please remember that not all students come from an English speaking background. Focus on whether the
relevant points have been clearly stated and not on the quality and sophistication of the language.
Questions 1 - 4
Question 1
Describe how DNA methylation is altered in cancer (maximum 300 words). In your answer include the
following points:
En el ADN existen dinucleótidos CpG que son la unión de citosina con guanina. Estos dinucleótidos se
encuentran en mayor medida en las regiones promotoras de genes, zonas de inicio de la transcripción
génica. En algunos casos la citosina está metilada formando 5′-metil-citosina. Esta metilación puede ser
normal a lo largo del ADN, pero en las zonas de islas CpG, si no hay metilación en esas zonas es un
indicador de que el sitio de transcripción se encuentra activado. Cuando estas islas CpG presentan una
elevada metilación se puede producir el silenciamiento de la transcripción del gen. En ciertos tipos de
genes, llamados supresores de tumores, una metilación excesiva en su región promotora, o sea las islas
CpG, puede suprimir la transcripción, evitando así que se expresen los genes de esa zona. Estos genes se
encargan de evitar errores en las células y su inactivación puede llegar a producir una división
descontrolada produciendo cáncer. En el 98% del genoma, las islas CpG aparecen una vez cada 100
dinucleótidos y se encuentran muy metilados con objeto de estructurar la cromatina nuclear en un estado
represivo que impida la transcripción de regiones poco útiles y potencialmente peligrosas del ADN, tales
como las secuencias que son repetitivas.
There are CpG dinucleotides that are the union of cytosine with guanine in DNA. These dinucleotides
are greater in the promoter regions of genes, gene transcription starting zones. In some cases the
cytosine is methylated forming 5′-methyl-cytosine. This methylation can be normal along the DNA,
but in areas of CpG Islands, if there is no methylation in these areas is an indicator that the site of
transcription is activated. When these CpG Islands have a high methylation can occur the silencing of
the transcription of the gene. In certain types of genes, called suppressor of tumors, an excessive
methylation in the promoter region, or CpG Islands, can suppress transcription, thus preventing
expressed genes in that area. These genes are responsible for avoiding mistakes in cells and
inactivation can cause an uncontrolled division producing cancer. In 98% of the genome, CpG islands
appear once every 100 dinucleotides and are very methylated with the aim of structuring the nuclear
chromatin in a repressive State that prevents transcription of unhelpful and potentially dangerous
regions of DNA, such as sequences that are repeated. Intergenic regions and repetitive elements use
to have their promotors methylated. When these promotors are unmethylated these regions are
expressed and some genes in this zone should not to be expressed, if that occurs it will cause
serious diseases.
Question 2
Describe how disruption of imprinting can contribute to cancer, using the example of the H19/Igf2 cluster
(maximum 200 words). In your answer include the following points:
Describe the methylation pattern of the paternal allele and how this determines Igf2 expression status
Describe the methylation pattern of the maternal allele and how this determines Igf2 expression status
Describe how imprinting at the H19/Igf2 cluster is disrupted in Wilm’s tumour
Explain how disrupting imprinting at the H19/Igf2 cluster contributes to cancer.
En las células normales, se expresan lgf2 y H19. Igf2 es un factor de crecimiento que es expresado solo
por el alelo paterno y el H19 es expresado desde el alelo maternal. Esto es controlado por una región de
control de impreso ICR la cual está metilada en el alelo paterno, pero no en el materno. Si ICR no se
metila en el alelo materno, se une a la proteína CTCF, provocando que no se exprese Igf2. En el alelo
paterno ICR sí está metilado por lo que se expresa lgf2.
Question 3
The Economist article “Cancer’s epicentre” describes several drugs that affect epigenetic processes. Explain
how Decitabine may be used to treat cancer, with reference to effects on the epigenome (maximum 150
words). In your answer include the following points:
Identify the class of epigenetic inhibitors that Decitabine belongs to
Describe the impact of Decitabine on DNA methylation
Describe how Decitabine can have an anti-tumour effect.
Question 4
Dr Stephen Baylin speculates in the Economist article that "epigenetic drugs altered the tumour cells in some
lasting way that made them more susceptible to standard chemotherapy." How can drugs that alter DNA
methylation have effects that last beyond the period of drug treatment? Discuss whether there are any periods
of development when you would avoid treating patients with such drugs (maximum 200 words). In your
answer include the following points:
Describe how altering DNA methylation can have enduring effects on the epigenome
Define what is meant by a sensitive period
Identify sensitive periods of development
Explain why treating patients during sensitive periods would be inadvisable.
La metilación de ADN es una marca epigenética que es mitóticamente heredable, así que esas alteraciones
pasan a las células hijas provocando que el efecto sea duradero. El periodo sensitivo está definido por los
sucesos ocurridos antes de que sean definidos y estabilizados mitóticamente los cambios epigenéticos y la
metilación de ADN en células somáticas. Tratar a pacientes con las drogas ya mencionadas podría
provocar modificaciones epigenéticas aberrantes y silenciar en el caso de los inhibidores de
metiltransferasas que inhiban la expresión de un gen necesario y como esto es mitóticamente heredable o
sea que estos patrones epigenéticos se transmiten por divisiones celulares, pasarían a las células hijas
influyendo en el desarrollo de enfermedades.
DNA methylation is an epigenetic mark that is mitotically heritable, so these changes are inherited to
daughter cells causing the effect is lasting. The sensitive period is defined by the events occurred before
epigenetic changes and DNA methylation in somatic cells are defined and stabilize mitotically. Treat
patients with the aforementioned drugs may cause aberrant epigenetic modifications and silence, in the
case of inhibitors of methyltransferases, the expression of a gene necessary. And as this is mitotically
heritable, ie these epigenetic marks are transmitted by cell divisions to daughter cells would influence the
development of cancer diseases.