Analysis of the t(3;8) of hereditary renal cell carcinoma: a palindrome-mediated translocation.

Autor: Kato T; Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA., Franconi CP; Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA., Sheridan MB; Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA., Hacker AM; Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA., Inagakai H; Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, Aichi, Japan., Glover TW; Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA., Arlt MF; Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA., Drabkin HA; Division of Hematology-Oncology, Medical University of South Carolina, Charleston, SC, USA., Gemmill RM; Division of Hematology-Oncology, Medical University of South Carolina, Charleston, SC, USA., Kurahashi H; Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, Aichi, Japan., Emanuel BS; 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.
Jazyk: angličtina
Zdroj: Cancer genetics [Cancer Genet] 2014 Apr; Vol. 207 (4), pp. 133-40. Date of Electronic Publication: 2014 Mar 18.
DOI: 10.1016/j.cancergen.2014.03.004
Abstrakt: 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.
(Copyright © 2014 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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