A novel stop codon mutation in STK11 gene is associated with Peutz-Jeghers Syndrome and elevated cancer risk: a case study

Abstract

Based on the analysis of patients with Peutz-Jeghers syndrome (PJS), Serine threonine kinase11 (STK11) is known as a tumor suppressor gene, which is involved in cell polarization, regulation of apoptosis, and DNA damage response. In this case report study, we examined STK11 gene sequencing in a 42-year-old woman with mucocuta neous pigmentation and positive family history. Endoscopy and colonoscopy showed >1000 polyps throughout the stomach/colon (PJ-type hamartomas). The larger polyp in the stomach was resected and the small bowel imaging detected multiple jejunum/ileum small polyps. The data released from the sequencing results revealed five alterations in exons 1 to 5. The major mutation in stop codon was reported as converted to the amino acid tryptophan (TRP) to tyrosine (TER). The TGG codon was converted to TAG by mutation. Finally, another novel mutation in STK11 stop codon as a 'de novo' variant was seen. It is predicted that stop codon mutations make the affected person susceptible to developing colorectal cancer.

Keywords: Genetic analysis; Novel mutation; Peutz-Jeghers syndrome (PJS); STK11gene; Sequencing.

Figure 1

The STK11 /AMPK/mTORC1-dependent regulation of protein translation. STK11 is a master kinase controlling 14 substrates, including AMPK. Following AMP binding to AMPK, this substrate is activated. AMPK activation directly phosphorylates TSC2 to inhibit mTORC1 activity

Figure 2

Genogram, pathology, and electropherogram of the examined patient. (A) The genogram showing an isolated PJS patient. Roman numerals indicate generations and Arabic numerals reveal individuals. Squares = males, circles = females. The affected individuals are denoted by solid symbols and unaffected individuals are represented by open symbols. The index patient is indicated by an arrow. (B) View of tissue sections stained with hematoxylin-eosin of gastrointestinal polyp specimens, confirming hamartomatous polyps. (C) Sanger sequencing revealing a heterozygous substitution new mutation, in 5 exon structure of STK11 gene