QuestionSBA
QuestionChoice
In those with melanoma, 50-60% will have a mutation in the B-RAF gene. This gene plays a crucial role in activating the MAP - Kinase pathway which drives cellular proliferation.

This is activated by K-RAS upstream to promote cellular proliferation.
10005862
b
B- RAF
QuestionChoice
TERT mutations are responsible for the transformation of the intermediate lesion to melanoma in situ.

TERT works with the enzyme telomerase to increase the length of chromosomes. These are mainly inactive in adults. Mutation results in increased expression and activation of this protein. Mutations are most likely to occur in sun-exposed areas and with B-RAF and CDKN2A mutations.

TERT promoter region mutations are seen in 30% of malignant melanomas.
10005864
d
TERT
QuestionChoice
BRCA genes are tumour suppressor genes and help repair damaged DNA that has had double-strand breaks.

In homologous recombination, BRCA1 and 2 associate themselves at the terminal where the strand break is. These, along with other proteins guide them to other undamaged DNA and by the complementary pairing of the nucleotide bases the DNA strand is reformed and stuck together.

When mutations occur, they increase the risk of developing cancers such as breast, ovarian, colorectal, pancreatic and prostate cancer.
10005865
e
BRCA 1
QuestionChoice
Responsible for 60-80% of sporadic cancers.

Beta-catenin within the colonic crypt cells binds to DNA and promotes transcription. APC targets Beta-catenin for destruction to prevent transcription and proliferation.

When APC is mutated beta-catenin is not degraded and is free to go into the nucleus and promote proliferation.

Adenomas develop which are precursors for cancer.
10005861
a
APC
QuestionChoice
This oncogene is the most frequently mutated gene in human cancers.

Ras is responsible for the downstream signalling of cellular proliferation in the MAP-kinase pathway.

When mutated, Ras becomes permanently active resulting in uncontrolled proliferation.

This is seen in Colorectal cancer (CRC) for transforming adenoma into a late adenoma.
10005863
c
K-RAS
Concept
Chapter
2693
4315
Molecular basis of cancer
Topic
182
Cancer Biology
13719
70 year old male has been diagnosed with bowel cancer in the sigmoid colon.

There is no family history of cancers and he has no significant past medical history.

Which of these is likely to mutate first to produce an early adenoma?
a