TY - JOUR
T1 - Analysis of the t(3;8) of hereditary renal cell carcinoma
T2 - A palindrome-mediated translocation
AU - Kato, Takema
AU - Franconi, Colleen P.
AU - Sheridan, Molly B.
AU - Hacker, April M.
AU - Inagakai, Hidehito
AU - Glover, Thomas W.
AU - Arlt, Martin F.
AU - Drabkin, Harry A.
AU - Gemmill, Robert M.
AU - Kurahashi, Hiroki
AU - Emanuel, Beverly S.
N1 - Funding Information:
The authors wish to thank Laura K. Conlin and Sharon E. Plon for providing technical assistance and invaluable reagents. These studies were supported by CA039926 , from the National Cancer Institute (B.S.E.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. The studies were also supported by funds from the Charles E.H. Upham Chair in Pediatrics (B.S.E.). One of the authors, T.K., was supported by a JSPS Postdoctoral Fellowship for Research Abroad.
PY - 2014/4
Y1 - 2014/4
N2 - 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.
AB - 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.
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U2 - 10.1016/j.cancergen.2014.03.004
DO - 10.1016/j.cancergen.2014.03.004
M3 - Article
C2 - 24813807
AN - SCOPUS:84901604510
VL - 207
SP - 133
EP - 140
JO - Cancer genetics
JF - Cancer genetics
SN - 2210-7762
IS - 4
ER -