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. 2003 Aug;73(2):404-11.
doi: 10.1086/377109. Epub 2003 Jul 3.

Germline PTEN promoter mutations and deletions in Cowden/Bannayan-Riley-Ruvalcaba syndrome result in aberrant PTEN protein and dysregulation of the phosphoinositol-3-kinase/Akt pathway

Xiao-Ping Zhou  1 , Kristin A Waite, Robert Pilarski, Heather Hampel, Magali J Fernandez, Cindy Bos, Majed Dasouki, Gerald L Feldman, Lois A Greenberg, Jennifer Ivanovich, Ellen Matloff, Annette Patterson, Mary Ella Pierpont, Donna Russo, Najah T Nassif, Charis Eng
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Germline PTEN promoter mutations and deletions in Cowden/Bannayan-Riley-Ruvalcaba syndrome result in aberrant PTEN protein and dysregulation of the phosphoinositol-3-kinase/Akt pathway (VSports app下载)

Xiao-Ping Zhou et al. Am J Hum Genet. 2003 Aug.

"VSports app下载" Abstract

Germline intragenic mutations in PTEN are associated with 80% of patients with Cowden syndrome (CS) and 60% of patients with Bannayan-Riley-Ruvalcaba syndrome (BRRS). The underlying genetic causes remain to be determined in a considerable proportion of classic CS and BRRS without a polymerase chain reaction (PCR)-detectable PTEN mutation. We hypothesized that gross gene deletions and mutations in the PTEN promoter might alternatively account for a subset of apparently mutation-negative patients with CS and BRRS. Using real time and multiplex PCR techniques, we identified three germline hemizygous PTEN deletions in 122 apparently mutation-negative patients with classic CS (N=95) or BRRS (N=27). Fine mapping suggested that one deletion encompassed the whole gene and the other two included exon 1 and encompassed exons 1-5 of PTEN, respectively. Two patients with the deletion were diagnosed with BRRS, and one patient with the deletion was diagnosed with BRRS/CS overlap (features of both). Thus 3 (11%) of 27 patients with BRRS or BRRS/CS-overlap had PTEN deletions VSports手机版. Analysis of the PTEN promoter revealed nine cases (7. 4%) harboring heterozygous germline mutations. All nine had classic CS, representing almost 10% of all subjects with CS. Eight had breast cancers and/or benign breast tumors but, otherwise, oligo-organ involvement. PTEN protein analysis, from one deletion-positive and five PTEN-promoter-mutation-positive samples, revealed a 50% reduction in protein and multiple bands of immunoreactive protein, respectively. In contrast, control samples showed only the expected band. Further, an elevated level of phosphorylated Akt was detected in the five promoter-mutation-positive samples, compared with controls, indicating an absence of or marked reduction in functional PTEN. These data suggest that patients with BRRS and CS without PCR-detected intragenic PTEN mutations be offered clinical deletion analysis and promoter-mutation analysis, respectively. .

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Figures

Figure 1
Figure 1
Real-time quantitative multiplex PCR results for 12 normal control subjects and 122 apparently mutation-negative individuals with CS and/or BRRS at PTEN exon 1. Normal control subjects showed 2−(ΔΔCT) values between 0.93 and 1.21. Patients with two copies of PTEN displayed values between 0.81 and 1.35, whereas patients with hemizygous deletions (one copy) had values between 0.45 and 0.60.
Figure 2
Figure 2
Genotyping results for the three patients with BRRS and/or CS with hemizygous PTEN deletions.
Figure 3
Figure 3
Germline PTEN promoter mutations and polymorphisms found in probands with CS
Figure 4
Figure 4
Aberrant PTEN protein species and increased phosphorylation of Akt in promoter-mutation samples. Samples from patients with promoter mutations (P), a patient who is PTEN-mutation negative (N), and normal control subjects (C) were analyzed. A, Western analysis for PTEN protein. Open arrows indicate the expected molecular weight of PTEN; closed arrows indicate the slower migrating band. B, Western analysis for P-Akt.
See this image and copyright information in PMC

References

Electronic-Database Information

    1. Online Mendelian Inheritance in Man (OMIM), http://www.ncbi.nlm.nih.gov/Omim/ (for CS, BRRS, PS, and PTEN/MMAC1/TEP1)

References

    1. Ahmed SF, Cheng A, Dovey L, Hawkins JR, Martin H, Rowland J, Shimura N, Tait AD, Hughes IA (2000) Phenotypic features, androgen receptor binding, and mutational analysis in 278 clinical cases reported as androgen insensitivity syndrome. J Clin Endocrinol Metab 85:658–665 - PubMed
    1. Arch EM, Goodman BK, Van Wesep RA, Liaw D, Clarke K, Parsons R, McKusick VA, Geraghty MT (1997) Deletion of PTEN in a patient with Bannayan-Riley-Ruvalcaba syndrome suggests allelism with Cowden disease. Am J Med Genet 71:489–493 - V体育平台登录 - PubMed
    1. Eng C (2000) Will the real Cowden syndrome please stand up: revised diagnostic criteria. J Med Genet 37:828–830 - PMC - PubMed
    1. Gorlin RJ, Cohen MM Jr, Condon LM, Burke BA (1992) Bannayan-Riley-Ruvalcaba syndrome. Am J Med Genet 44:307–314 - PubMed
    1. Liaw D, Marsh DJ, Li J, Dahia PL, Wang SI, Zheng Z, Bose S, Call KM, Tsou HC, Peacocke M, Eng C, Parsons R (1997) Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome. Nat Genet 16:64–67 - PubMed

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