Molecular Cytogenetics - Latest Comments

Complex translocation versus independent abnormalities in chronic myeloid leukemia

Juan Ramon Gonzalez Garcia — 2012-06-18T13:36:12Z

Reyna Lucia Barajas Torres and Juan Ramon Gonzalez Garcia.
Division de Genetica, Centro de Investigacion Biomedica de Occidente, Instituto Mexicano del Seguro Social. Guadalajara, Jalisco, Mexico. reyna_bio@hotmail.com, jrgg_gene@hotmail.com

To the editor: Yokota et al. [1] reported a complex rearrangement in a patient with chronic myeloid leukemia (CML). Firstly, these authors established by G-banding the presence of two independent translocations t(7;11;9)(q22;q13;q34) and t(9*;22)(q34;q11.2). Then, the authors interpreted their fluorescence in situ hybridization (FISH) results with the LSI BCR/ABL ES Dual Color Translocation Probe Set (Vysis, Inc.) as a five-way translocation t(7;11;9;22;9*)(q22;q13;q34;q11.2;q34). However, the hypothesis of two independent translocations cannot be excluded with these FISH findings. That is, the standard t(9*;22) with deletion of 5¿ ABL sequences (including ASS gene) will render a FISH pattern of 1 green-red fused signal on the der(22) and no signal on the der(9*); additionally, the independent three-way translocation t(7;11;9)(q22;q13;q34) with the breakpoint upstream from 5¿ ABL gene but downstream from 3¿ or within the ASS gene complete the observed pattern of signals, namely, a faint red signal on the der(9)t(9;11) and a brighter signal on the der(7)t(7;22). A FISH study with LSI BCR/ABL + 9q34 Tricolor, Dual Fusion Translocation probe (Vysis, Inc.) could be the best option to test this hypothesis since this approach may let to visualise the putative 5¿ ABL deletion.
There are at least other eight reported CML cases with a five-way translocation additional to those included in the table 1 [1]. They are 46,XX,t(1;22;9;5;3)(p32;q11;q34;q12;p13) (case 2) [2]; t(4;5;7;9;22)(q21;p13;p12;q34;q11) (case 35) [3]; t(6;10;9;9;22)(q24;p15;p13;q34;q11) (case 1) [4]; t(1;20;9;22;4)(q42;q12;q34;q11;q12) (case 1) [5]; t(6;9;22;11;20)(p11;q34;q11;q13;q11) (case 9) [6]; and, t(3;9;22;14;17)(p22;q34;q11;q13;q12); t(9;22;12;17;17)(q34;q11;q15;q11;q23); and t(1;22;9;15;1)(q21;q11;q34;q22;q21) (cases 9, 31, and 62, respectively) [7].
It is really important to establish the correct karyotype in order to avoid future misinterpretations and wrong citations. An example of this is the patient # 15 reported by Bennour et al. [8] which is registered in an important public database [9] as having the complex karyotype 46,XX,t(1;1;2;9;12;13;22)(q24;q31;p21;q34;p12;p12;q11). According to their FISH studies such abnormality had to be settled as 46,XX,t(1;2),t(1;9;22),t(12;13) showing the occurrence of three independent translocations rather than a complex rearrangement. This mistake misleads the knowledge and hinders the understanding of the CML etiopathology.
Endnotes
*The editorial system did not allow to underline this character as recommended by the International System for Human Cytogenetic Nomenclature (2009).
The original karyotype of case 31 in reference 7 was amended according to the breakpoint description.
References
1. Yokota S, Nakamura Y, Bessho MA: Novel five-way translocation t(7;11;9;22;9*)(q22;q13;q34;q11.2;q34) involving Ph chromosome in a patient of chronic myeloid leukemia: a case report. Mol Cytogenet 2012, 5:20.
2. Hagemeijer A, de Klein A, Gödde-Salz E, Turc-Carel C, Smit EM, van Agthoven AJ, Grosveld GC: Translocation of c-abl to "masked" Ph in chronic myeloid leukemia. Cancer Genet Cytogenet 1985, 18:95-104.
3. Michalová K, Musilová J, Koudelová Z, Placerová J, Matuchová L: Cytogenetic study of chronic myeloid leukemia. Neoplasma 1988, 35:571-581.
4. Zaccaria A, Testoni N, Tassinari A, Celso B, Rassool F, Saglio G, Guerrasio A, Rosti G, Tura S: Cytogenetic and molecular studies in patients with chronic myeloid leukemia and variant Philadelphia translocations. Cancer Genet Cytogenet 1989, 42:191-201.
5. Teixeira MR, Micci F, Dietrich CU, Heim S: Detailed genome-wide screening for inter- and intrachromosomal abnormalities by sequential G-banding and RxFISH color banding of the same metaphase cells. Cancer Genet Cytogenet 2000, 119:94-101.
6. Richebourg S, Eclache V, Perot C, Portnoi MF, Van den Akker J, Terré C, Maareck O, Soenen V, Viguié F, Laï JL, Andrieux J, Corm S, Roche-Lestienne C; Fi-LMC Group: Mechanisms of genesis of variant translocation in chronic myeloid leukemia are not correlated with ABL1 or BCR deletion status or response to imatinib therapy. Cancer Genet Cytogenet 2008, 182:95-102.
7. Fabarius A, Leitner A, Hochhaus A, Müller MC, Hanfstein B, Haferlach C, Göhring G, Schlegelberger B, Jotterand M, Reiter A, Jung-Munkwitz S, Proetel U, Schwaab J, Hofmann WK, Schubert J, Einsele H, Ho AD, Falge C, Kanz L, Neubauer A, Kneba M, Stegelmann F, Pfreundschuh M, Waller CF, Spiekermann K, Baerlocher GM, Lauseker M, Pfirrmann M, Hasford J, Saussele S, et al.: Impact of additional cytogenetic aberrations at diagnosis on prognosis of CML: long-term observation of 1151 patients from the randomized CML Study IV. Blood 2011, 118:6760-6768.
8. Bennour A, Sennana H, Laatiri MA, Elloumi M, Khelif A, Saad A: Molecular cytogenetic characterization of variant Philadelphia translocations in chronic myeloid leukemia: genesis and deletion of derivative chromosome 9. Cancer Genet Cytogenet 2009, 194:30-37.
9. Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer (2012). Mitelman F, Johansson B, and Mertens F (Eds). [http://cgap.nci.nih.gov/Chromosomes/Mitelman]. Accessed May 22, 2012.

Correction of proband's karyotype.

Emmanouil Manolakos — 2011-06-06T10:57:52Z

In the Results section: The karyotype of the proband was defined as follows: 46,XY.ish der(15)(15pter->15q11.2::22q11.2->22qter)t(15;22)(q11.2;q11.2)mat(TUPLE-,TBX1-).

Correction to typographical error

Michael B. Petersen — 2010-03-06T15:50:17Z

"We apologize for the typographical error in the cited reference [5] in the published manuscript. "Mattina T, Concetta SP, Grossfeld P: Jacobsen syndrome. Orphanet J Rare Dis 2009, 4:9" should read "Mattina T, CS Perrotta, Grossfeld P: Jacobsen syndrome. Orphanet J Rare Dis 2009, 4:9"

Full Steam Ahead

H.-Ulli Weier — 2010-03-06T15:47:23Z

Full Steam Ahead – The Unsinkable Journey of Interphase Cytogenetics.

Usually, I do not submit comments on review articles. Thus, I hope you forgive me, if this comment turns out to be a bit too wordy. Yet, it’s my great pleasure to bring to your attention this review article describing the present state of interphase cytogenetics and recent developments in the field.
The BMC - Molecular Cytogenetics article summarizes relevant developments in interphase analysis from the dark days of interphase cytogenetics (the 1980’ies), when only few probes and techniques in more-or-less-in-their infancy existed to the present state. Quite frankly, Dr. SG Vorsanova and her colleagues, Drs. YB Yorov and IY Iourov, did no less than an outstanding job in providing an overview of what technologies are available nowadays to the basic and advanced clinical or research laboratory. Being widely recognized experts in the field of cerebral/neuronal aneuploidy, they took it upon themselves to provide the reader with an in-depth review of state-of-the-art technologies for the chromosomal analysis of interphase cell nuclei in various types of tissue ranging from ovarian to extra-embryonic to fully differentiated adult tissues.
There are two important areas which, in my opinion, provide uniqueness and strength to this paper: the authors provide numerous educational illustrations which emphasize their major points of technical, FISH-based approaches to interphase analysis, and they provide an extensive list of reference articles.

This may not be an article you glance over and file. This may, however, be the article you keep at arm’s reach for easy reference or select for classroom teaching.

From the proof of concept to the application

Alain Bernheim — 2009-04-30T07:37:26Z

This superb paper clearly demonstrates a condensation asymetry between R and G bands that are intimely linked to the functionnal structure of the genome. It shows also that chromosome banding and sequence are not mathematicaly linked.
There is a need to address the exact localization and spliting of tiling probes (BAC or smaller) on human genomes (male and female) to assign each bit of the complete sequence to the metaphasic and interphasic chromosomes in detail. This huge project is technically feasible via a consortium. But will be a scientific mobilisation ?