title: Analysis of the t(3;8) of hereditary renal cell carcinoma: a palindrome-mediated translocation.
abstract: It has emerged that palindrome-mediated genomic instability generates DNA-based rearrangements. The presence of palindromic AT-rich repeats (PATRRs) at the translocation breakpoints suggested a palindrome-mediated mechanism in the generation of several recurrent constitutional rearrangements: the t(11;22), t(17;22), and t(8;22). To date, all reported PATRR-mediated translocations include the PATRR on chromosome 22 (PATRR22) as a translocation partner. Here, the constitutional rearrangement, t(3;8)(p14.2;q24.1), segregating with renal cell carcinoma in two families, is examined. The chromosome 8 breakpoint lies in PATRR8 in the first intron of the RNF139 (TRC8) gene, whereas the chromosome 3 breakpoint is located in an AT-rich palindromic sequence in intron 3 of the FHIT gene (PATRR3). Thus, the t(3;8) is the first PATRR-mediated, recurrent, constitutional translocation that does not involve PATRR22. Furthermore, we detect de novo translocations similar to the t(11;22) and t(8;22), involving PATRR3 in normal sperm. The breakpoint on chromosome 3 is in proximity to FRA3B, the most common fragile site in the human genome and a site of frequent deletions in tumor cells. However, the lack of involvement of PATRR3 sequence in numerous FRA3B-related deletions suggests that there are several different DNA sequence-based etiologies responsible for chromosome 3p14.2 genomic rearrangements.
authors.affiliation: Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: Takema
authors.initials: T
authors.lastname: Kato
authors.affiliation: Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: Colleen P
authors.initials: CP
authors.lastname: Franconi
authors.affiliation: Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: Molly B
authors.initials: MB
authors.lastname: Sheridan
authors.affiliation: Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: April M
authors.initials: AM
authors.lastname: Hacker
authors.affiliation: Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, Aichi, Japan.
authors.forename: Hidehito
authors.initials: H
authors.lastname: Inagakai
authors.affiliation: Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Glover
authors.affiliation: Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Martin F
authors.initials: MF
authors.lastname: Arlt
authors.affiliation: Division of Hematology-Oncology, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Harry A
authors.initials: HA
authors.lastname: Drabkin
authors.affiliation: Division of Hematology-Oncology, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Gemmill
authors.affiliation: Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, Aichi, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kurahashi
authors.affiliation: Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA; Department of Pediatrics, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. Electronic address: beverly@mail.med.upenn.edu.
authors.forename: Beverly S
authors.initials: BS
authors.lastname: Emanuel
mesh_terms: D020856:AT Rich Sequence / Q000235:genetics; D017766:Acid Anhydride Hydrolases / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D002460:Cell Line; D056905:Chromosome Breakpoints; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D006801:Humans; D055029:Inverted Repeat Sequences / Q000235:genetics; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics; D017422:Sequence Analysis, DNA; D014178:Translocation, Genetic; D000099170:Bis(5'-adenosyl)triphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D009363:Neoplasm Proteins; D011956:Receptors, Cell Surface; D000099170:Bis(5'-adenosyl)triphosphatase; C114025:RNF139 protein, human
keywords: FRA3B; PATRR; Palindrome; renal cell carcinoma; translocation