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 language | English |
|---|---|
| Pages (from-to) | 133-140 |
| Number of pages | 8 |
| Journal | Cancer Genetics |
| Volume | 207 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 04-2014 |
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All Science Journal Classification (ASJC) codes
- Molecular Biology
- Genetics
- Cancer Research
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Analysis of the t(3;8) of hereditary renal cell carcinoma : A palindrome-mediated translocation. / Kato, Takema; Franconi, Colleen P.; Sheridan, Molly B.; Hacker, April M.; Inagakai, Hidehito; Glover, Thomas W.; Arlt, Martin F.; Drabkin, Harry A.; Gemmill, Robert M.; Kurahashi, Hiroki; Emanuel, Beverly S.
In: Cancer Genetics, Vol. 207, No. 4, 04.2014, p. 133-140.Research output: Contribution to journal › Article
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.
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.
UR - http://www.scopus.com/inward/record.url?scp=84901604510&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84901604510&partnerID=8YFLogxK
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 -