ROLE OF APC GENE IN COLORECTAL CANCER

DEVELOPMENT
BY ANUPAMA SUNNY 3053
INTRODUCTION
 Adenomatous polyposis coli (APC) is a protein that in humans is encoded by the APC gene
 APC is classified as a tumor suppressor gene. Tumor suppressor genes prevent the uncontrolled growth of cells that may result in
cancerous tumors. .
 Inactivation of adenomatous polyposis coli (APC),has been recognized as a key early event in up to 85% of sporadic CRCs
 in 25–30% of patients it is a de novo mutation, in others it is a family occurrence.
 Familial adenomatous polyposis (FAP) is an inherited autosomal-dominant syndrome caused by a germline mutation in
the APC gene10.
 In accordance with Knudson’s ‘two hit’ hypothesis, FAP patients with a germline APC mutation have a very high risk to acquire
an additional somatic APC mutation mainly in the colorectum, that will eventually lead to the development of multiple
adenomas, starting at adolescence, with nearly 100% progression to CRC by the age of 40, if left untreated 10,11,12. The site of the
'first hit' in the APC tumor suppressor gene has an impact on the type of the 'second hit' that will either cause APC loss of
heterozygosity
 OVERVIEW OF FUNCTION
APC is a classical tumor suppressor gene, playing a central role in the Wnt signaling cascade. APC is an integral part of the degradation
complex. Therefore dysfunctional APC gene will lead to increase in cellular levels of b-catenin and thereby cause increased
transcription of Wnt genes which are responsible for growth and proliferation of the cell.
 CLINICAL PRESENTATION

Clinical manifestations are uncommon in childhood and adolescence. The first manifestations are usually manifestations of colon
polyposis, especially anemia caused by occult bleeding. Sometimes non-specific symptoms such as constipation, diarrhea, abdominal
pain or palpable masses may appear first.
Tumors may also be present in duodenum and may progress to malignancy . They may also cause pancreatitis due to obstruction of the
papilla.
Extraintestinal manifestation like fibromas may also be present
DIFFERENT FORMS

• Attenuated FAP is a clinically milder form of the disease with fewer

polyps, older age at diagnosis (50- 55), and later development of
malignancies.
• Gardner syndrome is a variant in which the clinical picture is dominated
by extraintestinal symptoms.
• Gardner syndrome can be identified based on oral findings, including
multiple impacted and supernumerary teeth, multiple jaw osteomas that
give a "cotton-wool" appearance to the jaws, as well as multiple odontomas,
congenital hypertrophy of the retinal pigment epithelium (CHRPE), in
addition to multiple adenomatous polyps of the colon. Gardner syndrome is
also associated with familial adenomatous polyposis and may manifest as
aggressive fibromatosis (desmoid tumors) of the retroperitoneum.