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

Takema Kato, Colleen P. Franconi, Molly B. Sheridan, April M. Hacker, Hidehito Inagakai, Thomas W. Glover, Martin F. Arlt, Harry A. Drabkin, Robert M. Gemmill, Hiroki Kurahashi, Beverly S. Emanuel

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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.

Original languageEnglish
Pages (from-to)133-140
Number of pages8
JournalCancer Genetics
Volume207
Issue number4
DOIs
Publication statusPublished - 04-2014

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Kato, T., Franconi, C. P., Sheridan, M. B., Hacker, A. M., Inagakai, H., Glover, T. W., Arlt, M. F., Drabkin, H. A., Gemmill, R. M., Kurahashi, H., & Emanuel, B. S. (2014). Analysis of the t(3;8) of hereditary renal cell carcinoma: A palindrome-mediated translocation. Cancer Genetics, 207(4), 133-140. https://doi.org/10.1016/j.cancergen.2014.03.004