An intronic polymorphic deletion in the PTEN gene: implications for molecular diagnostic testing

• Published in: British journal of cancer Vol. 108; no. 2; pp. 438 - 441
• Main Authors: Sandell, S, Schuit, R J L, Bunyan, D J
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 05-02-2013; Nature Publishing Group
• Subjects: 631/208/737; 631/67/581; 692/699/67/1534; Bannayan-Riley-Ruvalcaba syndrome; Binding sites; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer; Cancer Research; Diagnostic tests; DNA Mutational Analysis; Drug Resistance; Epidemiology; Genetics & Genomics; genetics-and-genomics; Hamartoma Syndrome, Multiple - diagnosis; Hamartoma Syndrome, Multiple - genetics; Haplotypes; Humans; Kinases; Medical sciences; Molecular Diagnostic Techniques; Molecular Medicine; Mutation; Oncology; Polymorphism; PTEN Phosphohydrolase - genetics; Sequence Analysis, DNA; Sequence Deletion; Tumors; United Kingdom > UK; United States > US; Netherlands; polymorphism; intronic deletion; Cancerology; Genetic variability; Molecular diagnostic; Deletion; PTEN; Genotype; PTEN Gene; Medical screening; Tumor suppressor gene; Polymorphism
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2012.562

Background:
A cohort of 629 patients with suspected Bannayan–Riley–Ruvalcaba syndrome or Cowden syndrome was tested for mutations in the
PTEN
gene.
Methods:
Dosage analysis of
PTEN
was carried out using a
PTEN
-specific multiplex ligation-dependent probe amplification (MLPA) kit, whereas point mutation analysis was performed using direct sequencing.
Results:
Approximately 4% of the patients from the testing cohort were heterozygously deleted for the two MLPA probe-binding sites situated in intron 1. The same deletion was subsequently seen in ∼3% of 220 normal controls, and in patients from the testing cohort with a causative mutation elsewhere in the
PTEN
gene. Sequencing of the variant revealed an 899 bp deletion, the 3′ breakpoint of which is only 58 bp from the start of exon 2.
Conclusion:
Although all evidence suggests that the 899 bp deletion is a polymorphism with no clinical effect, it removes the binding sites of almost all published
PTEN
exon 2 forward primers, resulting in allelic loss during PCR.