t(14;18)-negative follicular lymphomas are associated with a high frequency of BCL6 rearrangement at the alternative breakpoint region

Keni Gu, Kai Fu, Smrati Jain, Zhongfen Liu, Javeed Iqbal, Min Li, Warren G. Sanger, Dennis D. Weisenburger, Timothy Charles Greiner, Patricia Aoun, Bhavana J Dave, Wing C. Chan

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Abstract

A frequent chromosomal translocation in mature B-cell non-Hodgkin lymphoma affects band 3q27 and results in the deregulation of the B-cell lymphoma 6 (BCL6) gene. Two breakpoint clusters have been described thus far, the major breakpoint region (MBR) and an alternative breakpoint region (ABR) that is located 245-285 kb 5′ to BCL6. Translocation at the MBR predominates in diffuse large B-cell lymphoma, whereas translocation at the ABR is reported to be frequently associated with grade 3B follicular lymphoma. However, translocation at the ABR has not been studied in a large series of follicular lymphomas, particularly t(14;18)-negative follicular lymphomas. Therefore, we studied BLC6 rearrangements at the MBR and ABR by using break-apart fluorescence in situ hybridization (FISH) probes in 142 cases of follicular lymphomas, including 63 t(14;18)-negative and 79 t(14;18)-positive cases. Conventional cytogenetic (karyotype) analysis was also performed in 58 of the 63 t(14;18)-negative cases. BCL6 rearrangement was found in 26% of t(14;18)-negative and 19% of t(14;18)-positive follicular lymphoma. t(14;18)-negative cases showed a high frequency of rearrangement at the ABR (12%) with an ABR/MBR ratio of 0.86, compared with only 5% with an ABR/MBR ratio of 0.36 in the t(14;18)-positive cases. BCL6 rearrangements were found in all grades of follicular lymphoma but were most frequent in grade 3 t(14;18)-negative follicular lymphoma (60%). FISH analysis had a higher sensitivity for detecting BCL6 rearrangements than conventional cytogenetics. In conclusion, BCL6 rearrangements occur at a similar frequency in t(14;18)-negative follicular lymphoma and diffuse large B-cell lymphoma. However, t(14;18)-negative follicular lymphoma appears to have a higher frequency of rearrangement at the ABR compared with t(14;18)-positive follicular lymphoma and diffuse large B-cell lymphoma. Therefore, it is important to perform FISH analysis with ABR to determine possible involvement of BCL6 rearrangement in follicular lymphoma, especially in t(14;18)-negative cases.

Original languageEnglish (US)
Pages (from-to)1251-1257
Number of pages7
JournalModern Pathology
Volume22
Issue number9
DOIs
StatePublished - Sep 1 2009

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Follicular Lymphoma
B-Cell Lymphoma
Lymphoma, Large B-Cell, Diffuse
Fluorescence In Situ Hybridization
Genetic Translocation
Cytogenetic Analysis
Karyotype
Cytogenetics
Non-Hodgkin's Lymphoma

Keywords

  • Alternative breakpoint region
  • BCL6 rearrangement
  • Fluorescence in situ hybridization
  • Follicular lymphoma
  • Major breakpoint region
  • t(14;18)

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

t(14;18)-negative follicular lymphomas are associated with a high frequency of BCL6 rearrangement at the alternative breakpoint region. / Gu, Keni; Fu, Kai; Jain, Smrati; Liu, Zhongfen; Iqbal, Javeed; Li, Min; Sanger, Warren G.; Weisenburger, Dennis D.; Greiner, Timothy Charles; Aoun, Patricia; Dave, Bhavana J; Chan, Wing C.

In: Modern Pathology, Vol. 22, No. 9, 01.09.2009, p. 1251-1257.

Research output: Contribution to journalArticle

Gu, Keni ; Fu, Kai ; Jain, Smrati ; Liu, Zhongfen ; Iqbal, Javeed ; Li, Min ; Sanger, Warren G. ; Weisenburger, Dennis D. ; Greiner, Timothy Charles ; Aoun, Patricia ; Dave, Bhavana J ; Chan, Wing C. / t(14;18)-negative follicular lymphomas are associated with a high frequency of BCL6 rearrangement at the alternative breakpoint region. In: Modern Pathology. 2009 ; Vol. 22, No. 9. pp. 1251-1257.
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abstract = "A frequent chromosomal translocation in mature B-cell non-Hodgkin lymphoma affects band 3q27 and results in the deregulation of the B-cell lymphoma 6 (BCL6) gene. Two breakpoint clusters have been described thus far, the major breakpoint region (MBR) and an alternative breakpoint region (ABR) that is located 245-285 kb 5′ to BCL6. Translocation at the MBR predominates in diffuse large B-cell lymphoma, whereas translocation at the ABR is reported to be frequently associated with grade 3B follicular lymphoma. However, translocation at the ABR has not been studied in a large series of follicular lymphomas, particularly t(14;18)-negative follicular lymphomas. Therefore, we studied BLC6 rearrangements at the MBR and ABR by using break-apart fluorescence in situ hybridization (FISH) probes in 142 cases of follicular lymphomas, including 63 t(14;18)-negative and 79 t(14;18)-positive cases. Conventional cytogenetic (karyotype) analysis was also performed in 58 of the 63 t(14;18)-negative cases. BCL6 rearrangement was found in 26{\%} of t(14;18)-negative and 19{\%} of t(14;18)-positive follicular lymphoma. t(14;18)-negative cases showed a high frequency of rearrangement at the ABR (12{\%}) with an ABR/MBR ratio of 0.86, compared with only 5{\%} with an ABR/MBR ratio of 0.36 in the t(14;18)-positive cases. BCL6 rearrangements were found in all grades of follicular lymphoma but were most frequent in grade 3 t(14;18)-negative follicular lymphoma (60{\%}). FISH analysis had a higher sensitivity for detecting BCL6 rearrangements than conventional cytogenetics. In conclusion, BCL6 rearrangements occur at a similar frequency in t(14;18)-negative follicular lymphoma and diffuse large B-cell lymphoma. However, t(14;18)-negative follicular lymphoma appears to have a higher frequency of rearrangement at the ABR compared with t(14;18)-positive follicular lymphoma and diffuse large B-cell lymphoma. Therefore, it is important to perform FISH analysis with ABR to determine possible involvement of BCL6 rearrangement in follicular lymphoma, especially in t(14;18)-negative cases.",
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T1 - t(14;18)-negative follicular lymphomas are associated with a high frequency of BCL6 rearrangement at the alternative breakpoint region

AU - Gu, Keni

AU - Fu, Kai

AU - Jain, Smrati

AU - Liu, Zhongfen

AU - Iqbal, Javeed

AU - Li, Min

AU - Sanger, Warren G.

AU - Weisenburger, Dennis D.

AU - Greiner, Timothy Charles

AU - Aoun, Patricia

AU - Dave, Bhavana J

AU - Chan, Wing C.

PY - 2009/9/1

Y1 - 2009/9/1

N2 - A frequent chromosomal translocation in mature B-cell non-Hodgkin lymphoma affects band 3q27 and results in the deregulation of the B-cell lymphoma 6 (BCL6) gene. Two breakpoint clusters have been described thus far, the major breakpoint region (MBR) and an alternative breakpoint region (ABR) that is located 245-285 kb 5′ to BCL6. Translocation at the MBR predominates in diffuse large B-cell lymphoma, whereas translocation at the ABR is reported to be frequently associated with grade 3B follicular lymphoma. However, translocation at the ABR has not been studied in a large series of follicular lymphomas, particularly t(14;18)-negative follicular lymphomas. Therefore, we studied BLC6 rearrangements at the MBR and ABR by using break-apart fluorescence in situ hybridization (FISH) probes in 142 cases of follicular lymphomas, including 63 t(14;18)-negative and 79 t(14;18)-positive cases. Conventional cytogenetic (karyotype) analysis was also performed in 58 of the 63 t(14;18)-negative cases. BCL6 rearrangement was found in 26% of t(14;18)-negative and 19% of t(14;18)-positive follicular lymphoma. t(14;18)-negative cases showed a high frequency of rearrangement at the ABR (12%) with an ABR/MBR ratio of 0.86, compared with only 5% with an ABR/MBR ratio of 0.36 in the t(14;18)-positive cases. BCL6 rearrangements were found in all grades of follicular lymphoma but were most frequent in grade 3 t(14;18)-negative follicular lymphoma (60%). FISH analysis had a higher sensitivity for detecting BCL6 rearrangements than conventional cytogenetics. In conclusion, BCL6 rearrangements occur at a similar frequency in t(14;18)-negative follicular lymphoma and diffuse large B-cell lymphoma. However, t(14;18)-negative follicular lymphoma appears to have a higher frequency of rearrangement at the ABR compared with t(14;18)-positive follicular lymphoma and diffuse large B-cell lymphoma. Therefore, it is important to perform FISH analysis with ABR to determine possible involvement of BCL6 rearrangement in follicular lymphoma, especially in t(14;18)-negative cases.

AB - A frequent chromosomal translocation in mature B-cell non-Hodgkin lymphoma affects band 3q27 and results in the deregulation of the B-cell lymphoma 6 (BCL6) gene. Two breakpoint clusters have been described thus far, the major breakpoint region (MBR) and an alternative breakpoint region (ABR) that is located 245-285 kb 5′ to BCL6. Translocation at the MBR predominates in diffuse large B-cell lymphoma, whereas translocation at the ABR is reported to be frequently associated with grade 3B follicular lymphoma. However, translocation at the ABR has not been studied in a large series of follicular lymphomas, particularly t(14;18)-negative follicular lymphomas. Therefore, we studied BLC6 rearrangements at the MBR and ABR by using break-apart fluorescence in situ hybridization (FISH) probes in 142 cases of follicular lymphomas, including 63 t(14;18)-negative and 79 t(14;18)-positive cases. Conventional cytogenetic (karyotype) analysis was also performed in 58 of the 63 t(14;18)-negative cases. BCL6 rearrangement was found in 26% of t(14;18)-negative and 19% of t(14;18)-positive follicular lymphoma. t(14;18)-negative cases showed a high frequency of rearrangement at the ABR (12%) with an ABR/MBR ratio of 0.86, compared with only 5% with an ABR/MBR ratio of 0.36 in the t(14;18)-positive cases. BCL6 rearrangements were found in all grades of follicular lymphoma but were most frequent in grade 3 t(14;18)-negative follicular lymphoma (60%). FISH analysis had a higher sensitivity for detecting BCL6 rearrangements than conventional cytogenetics. In conclusion, BCL6 rearrangements occur at a similar frequency in t(14;18)-negative follicular lymphoma and diffuse large B-cell lymphoma. However, t(14;18)-negative follicular lymphoma appears to have a higher frequency of rearrangement at the ABR compared with t(14;18)-positive follicular lymphoma and diffuse large B-cell lymphoma. Therefore, it is important to perform FISH analysis with ABR to determine possible involvement of BCL6 rearrangement in follicular lymphoma, especially in t(14;18)-negative cases.

KW - Alternative breakpoint region

KW - BCL6 rearrangement

KW - Fluorescence in situ hybridization

KW - Follicular lymphoma

KW - Major breakpoint region

KW - t(14;18)

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