A 32-year-old patient with familial adenomatous polyposis (FAP) and a desmoid tumor at the root of the mesentery undergoes total proctocolectomy. Which genetic alteration is associated with desmoid tumor formation in FAP and affects surgical strategy?
- A APC mutation in the region 3' to codon 1310 (codons 1310-2011) ✓
- B APC mutation upstream of codon 1310 (5' end)
- C KRAS mutation in exon 2
- D MLH1 promoter hypermethylation
Explanation
Desmoid tumors in FAP are strongly associated with APC mutations in the 3' region, particularly between codons 1310 and 2011 (with codon 1444 being the classical 'hot spot'). Mutations in this region confer an estimated 25-50 times higher risk of desmoid tumor formation. This genetic-phenotypic correlation is clinically important because patients with a family history of desmoid tumors or mutations in this region are advised to undergo proctocolectomy with ileal pouch-anal anastomosis earlier, and the risk of mesenteric desmoid must be considered before ileal J-pouch construction (mesenteric shortening may preclude pouch reach). Sulindac and anti-estrogens are used as first-line treatment for desmoids.
Reference: Bailey & Love's Short Practice of Surgery, 27th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.