Mosaic partial deletion of the PTEN gene in a patient with Cowden syndrome
- 437 Downloads
Cowden syndrome is an autosomal dominant condition caused by pathogenic mutations in the phosphatase and tensin homolog (PTEN) gene. Only a small proportion of identified pathogenic mutations have been reported to be large deletions and rearrangements. We report on a female patient with a previous history of breast ductal carcinoma in situ who presented to our institution for management of gastrointestinal hamartomatous polyposis. Although several neoplastic predisposition syndromes were considered, genetic evaluation determined that the patient met clinical diagnostic criteria for Cowden syndrome. Array-based comparative genomic hybridization was performed and revealed a mosaic partial deletion of the PTEN gene. Follow-up clinical history including bilateral thyroid nodules, dermatological findings, and a new primary “triple-negative” adenocarcinoma of the contralateral breast are discussed. We highlight the need for recognition and awareness of mosaicism as it may provide an explanation for variable phenotypic presentations and may alter the genetic counseling risk assessment of affected individuals and family members.
KeywordsBreast cancer Cowden syndrome Hamartomatous polyposis Mosaicism PTEN gene
The authors would like to acknowledge the Niehaus, Weissenbach, Southworth fund of the Robert and Kate Niehaus Clinical Cancer Genetics Initiative at MSKCC; the Sabin Family Research fund, the Tavel-Reznik Colorectal Cancer Research fund, and The Romeo Milio Lynch Syndrome Foundation. Z.K.S. is a Damon Runyon Cancer Research Foundation Clinical Investigator Award recipient.
Conflict of interest
The authors declare that they have no conflict of interest.
- 11.National comprehensive cancer network. Genetic/familial high-risk assessment: breast and ovarian. (Version 1.2013). http://www.nccn.org/professionals/physician_gls/pdf/genetics_screening.pdf. Accessed 9 April 2013
- 13.Zhou XP, Waite KA, Pilarski R et al (2003) 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. Am J Hum Genet 73(2):404–411. doi: 10.1086/377109 PubMedPubMedCentralCrossRefGoogle Scholar
- 15.Lachlan KL, Lucassen AM, Bunyan D, Temple IK (2007) Cowden syndrome and Bannayan Riley Ruvalcaba syndrome represent one condition with variable expression and age-related penetrance: results of a clinical study of PTEN mutation carriers. J Med Genet 44(9):579–585. doi: 10.1136/jmg.2007.049981 PubMedPubMedCentralCrossRefGoogle Scholar
- 25.Evans DG, Ramsden RT, Shenton A et al (2007) Mosaicism in neurofibromatosis type 2: an update of risk based on uni/bilaterality of vestibular schwannoma at presentation and sensitive mutation analysis including multiple ligation-dependent probe amplification. J Med Genet 44(7):424–428. doi: 10.1136/jmg.2006.047753 PubMedPubMedCentralCrossRefGoogle Scholar
- 29.Murgia A, Martella M, Vinanzi C, Polli R, Perilongo G, Opocher G (2000) Somatic mosaicism in von Hippel-Lindau Disease. Hum Mutat 15(1):114. doi: 10.1002/(sici)1098-1004(200001)15:1<114:aid-humu20>3.0.co;2-7 PubMedCrossRefGoogle Scholar
- 35.Ainsworth PJ, Chakraborty PK, Weksberg R (1997) Example of somatic mosaicism in a series of de novo neurofibromatosis type 1 cases due to a maternally derived deletion. Hum Mutat 9(5):452–457. doi: 10.1002/(sici)1098-1004(1997)9:5<452:aid-humu12>3.0.co;2-1 PubMedCrossRefGoogle Scholar
- 56.Perren A, Komminoth P, Saremaslani P et al (2000) Mutation and expression analyses reveal differential subcellular compartmentalization of PTEN in endocrine pancreatic tumors compared to normal islet cells. Am J Pathol 157(4):1097–1103. doi: 10.1016/s0002-9440(10)64624-x PubMedPubMedCentralCrossRefGoogle Scholar