title: Trilateral retinoblastoma in a patient with Peutz-Jeghers syndrome.
abstract: Germline loss of function mutations in tumor suppressor genes RB1 and LKB1/STK11 are associated with the autosomal dominant cancer predisposing syndromes familial retinoblastoma and Peutz-Jeghers syndrome (PJS), respectively. We present a rare case of a young woman with trilateral retinoblastoma diagnosed as an infant who survived and was then diagnosed with PJS as a teenager. There was no family history of either disorder. Analysis of the LKB1/STK11 gene sequence identified a germline frameshift mutation (c.107del) leading to a nonsense mutation near the N-terminus of the protein, confirming a clinical diagnosis of Peutz-Jeghers syndrome. Extensive RB1 gene analysis failed to detect germline mutations or deletions, and immunohistochemical analysis of her ocular tumors demonstrated nuclear staining of immunoreactive pRB. This result suggests that the RB1 gene is intact. We estimate the chance of trilateral retinoblastoma and PJS occurring in the same individual at approximately 1 in 134 billion live births, and we discuss the possibility that this case could be explained by a putative modifier of pRB action that is associated with the LKB1/STK11 pathway.
authors: Department of Molecular Pathology, Canterbury Health Laboratories, Christchurch, New Zealand. anthony.raizis@cdhb.govt.nz
authors: Anthony M
authors: AM
authors: Raizis
authors: David
authors: D
authors: Van Mater
authors: Lauri A
authors: LA
authors: Aaltonen
authors: Dietmar
authors: D
authors: Lohmann
authors: Michelle S
authors: MS
authors: Cheale
authors: Vivienne M
authors: VM
authors: Bickley
authors: Peter M
authors: PM
authors: George
authors: Yaolin
authors: Y
authors: Zhou
authors: Philip M
authors: PM
authors: Rosoff
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000293:Adolescent; D002648:Child; D018389:Codon, Nonsense; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D020411:Oligonucleotide Array Sequence Analysis; D010580:Peutz-Jeghers Syndrome / Q000150:complications* / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012175:Retinoblastoma / Q000150:complications* / Q000235:genetics; D017422:Sequence Analysis, DNA
chemical_list: D018389:Codon, Nonsense; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases