FISH-negative cryptic PML–RARA rearrangement detected by long-distance polymerase chain reaction and sequencing analyses: a case study and review of the literature

Kim, Min Jin; Cho, Sun Young; Kim, Myeong-Hee; Lee, Jae Jin; Kang, So Young; Cho, Eun Hae; Huh, Jungwon; Yoon, Hwi-Joong; Park, Tae Sung; Lee, Wooin; Marschalek, Rolf; Meyer, Claus

doi:10.1016/j.cancergencyto.2010.08.026

Cited by 54 publications

(46 citation statements)

References 20 publications

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“…These include t(14;17)(q22;q21), t(8;17)(p21;q21), t(1;17)(p36;q21), and t(7;17)(q36;q22). 21 These cases may represent cryptic rearrangements of the classic t(15;17) APL or one of the other known APL variants, or they may indeed represent new variants themselves. A case of a PML/RARA chimeric gene on chromosome 12 (t(12;15;17)(q24;q24;q11) has also been recently described.…”

Section: Cytogenetic and Molecular Featuresmentioning

confidence: 99%

“…21 Despite that cytogenetic studies may rarely be negative for t (15;17) in patients with APL, cytogenetic testing should be the first test performed in a patient suspected of having APL because the majority of patients possess t (15;17). In instances where cytogenetic testing is negative, rapid molecular tests such as fluorescence in situ hybridization, real-time polymerase chain reaction, and Southern blot analysis, as well as PML immunofluorescence, can be used to identify PML/RARA fusion.…”

Section: Cytogenetic and Molecular Featuresmentioning

confidence: 99%

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Acute Promyelocytic Leukemia: A Review and Discussion of Variant Translocations

Adams

Nassiri²

2015

Archives of Pathology &Amp; Laboratory Medicine

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The majority of patients with acute promyelocytic leukemia (APL) manifest the t(15;17)(q24.1;q21.2) translocation; however, a minor but significant proportion of patients with APL harbor complex, cryptic, or variant translocations, which typically involve RARA. With the exception of ZBTB16/RARA, these variants have similar morphologic and immunophenotypic features as classic APL. Study of the variant forms of APL not only gives insight into the pathogenesis of APL but also allows us to understand the mechanism of retinoid therapy. It is important to identify these cryptic and variant translocations because certain variants, including ZBTB16/RARA and STAT5B/RARA, are resistant to treatment with all-trans retinoic acid, arsenic trioxide, and anthracyclines. A cute promyelocytic leukemia (APL), comprising 5% to 8% of cases of acute myeloid leukemia (AML), is one of the best studied and understood hematopoietic malignancies. Unlike other forms of AML, APL is unique in that it can cause coagulopathy and death if not readily diagnosed.1,2 Morphologically classified as AML-M3 by the French-American-British (FAB) classification, APL is typically characterized by neoplastic proliferation of cells in the bone marrow with a promyelocytic phenotype and the balanced reciprocal translocation t(15;17) (q24.1;q21.2), which results in the expression of the promyelocytic leukemia (PML)-retinoic acid receptor-a (RARA) fusion protein.

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Section: Cytogenetic and Molecular Featuresmentioning

confidence: 99%

Section: Cytogenetic and Molecular Featuresmentioning

confidence: 99%

Acute Promyelocytic Leukemia: A Review and Discussion of Variant Translocations

Adams

Nassiri²

2015

Archives of Pathology &Amp; Laboratory Medicine

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“…A FISH-negative cryptic PML/RAR α rearrangement detected by long-distance PCR and sequencing analyses has also been reported [90]. Therefore, FISH analysis should be conducted, if the morphologic, cytogenetic, and molecular findings are inconsistent.…”

Section: Future Prospects and Concluding Remarksmentioning

confidence: 99%

Cancer Cytogenetics: Methodology Revisited

Wan

2014

Ann Lab Med

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The Philadelphia chromosome was the first genetic abnormality discovered in cancer (in 1960), and it was found to be consistently associated with CML. The description of the Philadelphia chromosome ushered in a new era in the field of cancer cytogenetics. Accumulating genetic data have been shown to be intimately associated with the diagnosis and prognosis of neoplasms; thus, karyotyping is now considered a mandatory investigation for all newly diagnosed leukemias. The development of FISH in the 1980s overcame many of the drawbacks of assessing the genetic alterations in cancer cells by karyotyping. Karyotyping of cancer cells remains the gold standard since it provides a global analysis of the abnormalities in the entire genome of a single cell. However, subsequent methodological advances in molecular cytogenetics based on the principle of FISH that were initiated in the early 1990s have greatly enhanced the efficiency and accuracy of karyotype analysis by marrying conventional cytogenetics with molecular technologies. In this review, the development, current utilization, and technical pitfalls of both the conventional and molecular cytogenetics approaches used for cancer diagnosis over the past five decades will be discussed.

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“…To our knowledge, 5 cases have been described, including the one with atypical fusion transcripts between PML exon 4 and RARA exon 3 (table 1) [4,7,8,9]. One reported case showed both an in-frame and an out-of-frame fusion of PML exon 4 and RARA exon 3 fusion transcript, while 3 other cases displayed only out-of-frame fusion transcripts.…”

Section: Figmentioning

confidence: 99%

“…The LD-PCR method was used to further characterize this unusual PML/RARA rearrangement which has been previously described by our research group [3,4,5,6]. It was used to determine the genomic PML/RARA fusion site.…”

Section: Figmentioning

confidence: 99%