Investigative case-based learning
“Gut instinct”
Reef, Joy, Divya, Kim
Case study:
Jun Ming was waiting to see a doctor at the National Cancer Centre Singapore. He was
diagnosed with Gastric cancer. Over the last few days, his pain had not eased despite the
chemotherapy that he went through last month.
Nurse: Queue number 234679.
Jun Ming stood up and went into the consultation room.
Doctor: How are you? I have read your CT scan and it seems as though the chemotherapy has
not worked well on you. This can happen due to individual genetic variability.
Jun Ming: Is there any alternative treatment options?
Doctor: Yes. I have sent your tissues to the lab to analyze whether you have any mutations in
some important genes. If the test results are positive, we could prescribe drugs that target
specifically for the mutated genes which will be a much more targeted treatment, specialised for
you. The results should be out this afternoon, I will keep you informed.
3 days ago........
The research assistant Jane obtained the tissue sample from the doctor and was tasked to
perform the analysis for four genes: A, B, C and D. She knows that certain mutations will not
lead to cancer, only mutations that cause structural changes of the proteins may result in cancer.
But she needs to know the sequence and any harmful mutation present in the four genes. With
Jun Ming's tissue, she has extracted DNA and planned to carry out: Polymerase Chain Reaction
(PCR), gel electrophoresis and sequencing of the four genes.
Case Analysis:
1. Recognise potential issues and major topics in the case. What is this case about?
Underline terms or phrases that seem to be important to understanding this case.
Then list three or four biology-related topics or issues in the case.
a)_______________________________________________________________
b)_______________________________________________________________
c)_______________________________________________________________
d)_______________________________________________________________
2. What specific questions do you have about these topics?
In your group, list what you already know about this case in the ‘What Do I know?’ column.
List questions you would like to learn more about in ‘What Do I Need to Know?’ column.
What Do I Know?
What Do I Need to Know?’
Suggested answers: (For teacher use)
What do we know:
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Jun Ming was diagnosed with gastric cancer
Jun Ming's last chemotherapy did not work well
Doctor sent Jun Ming's tissue for analysis on mutations, and if it is found that Jun Ming
has certain mutations on some proto-oncogenes, the doctor will prescribe specific drugs
for targeted treatment for Jun Ming
Research assistant Jane was tasked to perform analysis for four genes: A, B,C and D
Certain mutations will not lead to cancer. Only mutations that cause structural changes
of the proteins may result in cancer
Jane planned to carry out PCR, gel electrophoresis and sequencing of the four genes
What do we need to know:
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What is gastric cancer (GC)? What are the causes and symptoms of GC?
What are the current treatments available for GC; their advantages and disadvantages?
what is target therapy?
Why would the doctor choose some specific genes to analyze? Are they associated with
GC?
What is PCR, gel electrophoresis and sequencing?
Learning objectives (H2 Syllabus) :
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Learn the general information of GC
Understand and describe that cancer is a multistep process.
Understand and describe three techniques: PCR, Gel electrophoresis and Sequencing
through simulation
Explain how gel electrophoresis is used to analyse DNA.
Analyse the mutation status of the genes based on the sequence given and decide on
which gene may cause harmful effect to GC (oncogenes and tumour suppressor genes)
Learning tasks:
Task 1:
Gastric cancer
http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001270/
http://www.cancer.gov/cancertopics/types/stomach
Gapminder.org
Targeted therapy
http://www.cancer.gov/cancertopics/factsheet/Therapy/targeted
Students will read through the websites and answer the following questions:
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What is gastric cancer?
What are the general causes of GC?
What are the current treatment of GC?
what is targeted therapy?
Task 2:
Simulations
PCR:
http://learn.genetics.utah.edu/content/labs/pcr/
Gel electrophoresis:
http://learn.genetics.utah.edu/content/labs/gel/
www.scq.ubc.ca/dna-restriction-digest-and-gel-electrophoresis-a-virtual-lab
Sequencing:
http://www.pbs.org/wgbh/nova/genome/sequencer.html
Students will play with the simulation and answer the following questions:
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What is the function of PCR?
What are the components for PCR reactions?
Describe each stages of PCR in details
What is the purpose for gel electrophoresis?
How does gel electrophoresis work?
What are the components/materials required to perform sequencing?
Task 3:
The DNA Sequences for gene A, B C and D from Jun Ming’s tissue and from normal samples
are given in the appendix A.
Use the blast program provided below to align the sequences for each gene between Jun
Ming’s tissue and normal tissues and look for any possible mutations (Teacher to
demonstrate).
http://www.ebi.ac.uk/Tools/msa/clustalo/
Use the program below to translate the DNA sequences from Jun Ming’s tissue and from normal
samples into amino acid sequences (Teacher to demonstrate).
http://web.expasy.org/translate/
Analyze whether the DNA mutation lead to any amino acid changes by align the amino acid
sequences using the link below.
http://www.ebi.ac.uk/Tools/msa/clustalo/
Decide whether the doctor should target on the gene based on the mutation analysis and why?
Each group is designated to analyze one gene.
Task 4:
Design an online poster (use the link provided below) based on task 1-3 and present to the
class in the next session.
http://www.glogster.com
Implementation:
Duration: 120 mins
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Teacher to ask the students to form into groups of 4 or 5 (total 4 groups).
Teacher to introduce the scenario and ask students to discuss among their groups for
case analysis (what they know/what they need to know)
Teacher to introduce the tasks to the students and demonstrate the sequence
alignments
Teacher to assign each group with one gene
Students will perform the tasks within the group and design an online poster to present
in next session.
Rubrics for Assessment
Rubrics for Assessment of Group Poster (25 marks)
Criteria
Below
expectations
Approaching
Expectations
Meeting
Expectations
Exceeding
Expectations
Marks
0-1 marks
2 marks
3-4 marks
5 marks
Depth and
Breadth in the
analysis of the
case study
Analysis lacks
coverage in depth
and breadth.
Analysis
somewhat lacks
coverage in
depth and
breadth.
Analysis has
sufficient
coverage In
depth and
breadth.
Analysis has good
coverage in depth
and breadth.
Explanation
 Clarity
 Accuracy
&
Precision
in the Use
of
terminologi
es
Distracting errors
in clarity and
accuracy in the
use of
terminologies or
the lack of use of
precise scientific
description in the
poster.
A few errors in in
clarity and
accuracy in the
use of
terminologies or
the lack of use of
precise scientific
description in the
poster.
Generally clear in
explanation and
correct use of
appropriate
terminologies
and scientific
description in the
poster.
Clear in
explanation and
precise use of
terminologies in
the description in
the presentation
with no errors
made.
Content
 Relevance
Irrelevant details
given.
Some irrelevant
details given.
Most details are
relevant.
All details are
relevant.
Organisation
of Ideas
 Logical
sequence
 Fluency
Poster is poorly
organised and is
not fluent and
coherent.
Poster is
somewhat
organized, but
not fluent and
coherent.
Poster is
organized, fluent
and coherent.
Poster is well
organised, fluent
and coherent.
Creativity of
Design of
Glogster
Multimedia chosen
does not support
presentation
of
information.
Multimedia
chosen
somewhat
supports
presentation
information.
Multimedia
chosen supports
presentation
of
information.
Multimedia chosen
greatly enhances
presentation
of
information.
An
adequate
range
of
presentation
materials is used.
A diverse range of
presentation
materials
video,
powerpoint, picture
collages etc are
used in Glogster
produced.
A limited range of
presentation
materials is used.
of
A limited range
of
presentation
materials is used.
Rubrics for Assessment of Group Presentation (15 marks)
Criteria
Below
expectations
Approaching
Expectations
Meeting
Expectations
Exceeding
Expectations
Marks
0-1 marks
2 marks
3-4 marks
5 marks
Presentation is
poorly organised
and is not fluent
and coherent.
Presentation is
somewhat
organized, but
not fluent and
coherent.
Presentation is
organized, fluent
and coherent.
Presentation is
organised, fluent
and coherent.
Presentation is
completed within
the time limit.
Distracting errors
in clarity and
accuracy in the
use of
terminologies or
the lack of use of
precise scientific
description in the
presentation.
A few errors in in
clarity and
accuracy in the
use of
terminologies or
the lack of use of
precise scientific
description in the
presentation.
Generally clear in
explanation and
correct use of
appropriate
terminologies
and scientific
description in the
presentation.
Clear in
explanation and
precise use of
terminologies in
the description in
the presentation
with no errors
made.
Presenters are not
able to respond to
the questions i.e.
provide irrelevant
answers.
Presenters are
somewhat able
to respond to the
questions i.e.
answered only
one question
correctly.
Presenters are
able to respond
well to the
questions i.e.
answered most of
the questions
correctly.
Presenters are
able to respond
very well to the
questions i.e.
answered all
questions
correctly.
Coherence
Content
 Clarity
 Accuracy &
Precision in
the Use of
terminologi
es.
Q&A
21st Century competencies:

Critical and inventive thinking
1. Sound reasoning and decision making
2. Explore possibilities and generate ideas

Communication, collaborations and information skills
1. Manages, creates and shares digital information thoughtfully, ethically and responsibly
2. Communicates and collaborates effectively
 Civic literacy, global awareness and cross cultural skills
1. Aware of global issues and trends
2. Aware of community and national issues and plays a part to improve the community and nation
Appendix A
Gene A:
DNA sequence from Jun Ming’s tissue:
TAC TCC CCT GCC CTC AAC AAG ATG TTT TGC CAA TAG GCCAAGACCTGCCCTGTGCAGCTG
TGGGTTGATTCCACACCCCCGCCCGGCACCCGCGTCCGCGCCATGGCCATCTACAAGCAG
TCACAGCACATGACGGAGGTTGTGAGGCGCTGCCCCCACCATGAGCGCTGCTCAGATAGC
GATG
Normal DNA sequence:
TAC TCC CCT GCC CTC AAC AAG ATG TTT TGC CAA CTGGCCAAGACCTGCCCTGTGCAGCTG
TGGGTTGATTCCACACCCCCGCCCGGCACCCGCGTCCGCGCCATGGCCATCTACAAGCAG
TCACAGCACATGACGGAGGTTGTGAGGCGCTGCCCCCACCATGAGCGCTGCTCAGATAGC
GATG
nucleotide: CTG-TAG
aa: L-STOP
Gene B:
DNA sequence from Jun Ming’s tissue:
TCC CCC TTG CCG TCC CAA GCA ATG GAT GAA
TTGATGCTGTCCCCGGACGATATTGAACAA
TGGTTCACTGAAGACCCAGGTCCAGATGAAGCTCCCAGAATGCCAGAGGCTGCTCCCCCC
GTGGCCCCTGCACCAGCAGCTCCTACACCGGCGGCCCCTGCACCAGCCCCCTCCTGGCCC
CTGTCATCTTCTGTCCCTTCCCAGAAAACCTACCAGGGCAGCTACGGTTTCCGTCTGGGC
TTCTTGCATTCTGGGACAGCCAAGTCTGTGACTTGCACG
Normal DNA sequence:
TCCCCCTTGCCGTCCCAAGCAATGGATGATTTGATGCTGTCCCCGGACGATATTGAACAA
TGGTTCACTGAAGACCCAGGTCCAGATGAAGCTCCCAGAATGCCAGAGGCTGCTCCCCCC
GTGGCCCCTGCACCAGCAGCTCCTACACCGGCGGCCCCTGCACCAGCCCCCTCCTGGCCC
CTGTCATCTTCTGTCCCTTCCCAGAAAACCTACCAGGGCAGCTACGGTTTCCGTCTGGGC
TTCTTGCATTCTGGGACAGCCAAGTCTGTGACTTGCACG
nucleotide: T-A
aa: D-L
Gene C:
DNA sequence from Jun Ming’s tissue:
GGTAATCTACTGGGACGGAACA CTTTGAGGTGCGTGTTTGTGCCTGTCCTGGGAGAGA
CCGGCGCACAGAGGAAGAGAATCTCCGCAAGAAAGGGGAGCCTCACCACGAGCTGCCCCC
AGGGAGCACTAAGCGAG
Normal DNA sequence:
GGTAATCTACTGGGACGGAACAG CTTTGAGGTGCGTGTTTGTGCCTGTCCTGGGAGAGA
CCGGCGCACAGAGGAAGAGAATCTCCGCAAGAAAGGGGAGCCTCACCACGAGCTGCCCCC
AGGGAGCACTAAGCGAG
nucleotide: G-deleted
aa: framshift
Gene D:
DNA sequence for gene D (from Jun Ming’s tissue):
CAT TGCCCAACAACACCAGCTCCTCTCCCCAGCCAAAGAAGAAACCACTGGATGGAGAAT
ATTTCACCCTTCAG ATCCGTGGGCGTGAGCGCTT
Normal DNA sequence for gene D:
CACTGCCCAACAACACCAGCTCCTCTCCCCAGCCAAAGAAGAAACCACTGGATGGAGAAT
ATTTCACCCTTCAG ATCCGTGGGCGTGAGCGCTT
nucleotide: C-T
aa: H-H
The end