STK11 – Familial Pancreatic Carcinoma

Familial pancreatic carcinoma (FPC) is defined by pancreatic cancer in a patient with at least two first-degree relatives affected in the absence of an identified genetic cause. Although germline mutations in STK11 (encoding LKB1) cause Peutz–Jeghers syndrome with high pancreatic cancer risk, evidence for STK11 in non‐syndromic FPC is sparse. A recent review listed STK11 among well-known hereditary pancreatic cancer susceptibility genes but did not report proband counts or segregating STK11 variants in FPC families (PMID:35163129). Likewise, the German FaPaCa series tested STK11 in 70 autosomal dominant kindreds but identified deleterious mutations only in BRCA2 and PALB2, not STK11 (PMID:21207249).

Functional studies demonstrate that LKB1 loss abrogates acinar polarity and triggers cystic neoplasms in pancreas-specific Stk11 knockout mice, modeling PJS-associated lesions and underscoring LKB1’s tumor suppressor role in the exocrine pancreas (PMID:18227155). Mechanistically, LKB1 haploinsufficiency impairs AMPK activation and epithelial organization. However, no STK11 variants have yet been documented in non-PJS FPC pedigrees, and further genetic screening in large FPC cohorts is required. Key Take-home: STK11 screening outside syndromic contexts remains of limited clinical utility for FPC at present.

References

• International journal of molecular sciences • 2022 • Molecular Features and Clinical Management of Hereditary Pancreatic Cancer Syndromes and Familial Pancreatic Cancer PMID:35163129
• Familial cancer • 2011 • German national case collection for familial pancreatic cancer (FaPaCa): ten years experience PMID:21207249
• Molecular and cellular biology • 2008 • Pancreatic LKB1 deletion leads to acinar polarity defects and cystic neoplasms PMID:18227155

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