Cancer Genetics and Cytogenetics 175 (2007) 89e90

Editorial

Commentary on ISCN 2005

It is amazing to think that the rapid development of thefield of human cytogenetics, which began with, and wasbased upon, the historic description of the correct numberof human chromosomes in 1956 by Tjio and Levan [1], al-ready called for a standardization of nomenclature by 1960.The introduction of banding techniques and the subsequentdevelopment and application of various FISH methodolo-gies and molecular cytogenetics, each required a furthermodification and enlargement of the International Systemof Human Cytogenetic Nomenclature (ISCN). The latestof these, ISCN 2005 [2], dealing with the ever-expandingbody of cytogenetic information based on new methodolo-gies, presents recommendations for the nomenclature ofchromosome changes under various conditions.

Now that cytogeneticists have gained experience withISCN 2005, some of its deficiencies have become apparent.I address two of these here, as someone personally involvedin the daily reporting of cytogenetic results as well as (as anassociate editor of Cancer Genetics and Cytogenetics) inthe editing of annotations used by authors to describe cyto-genetic and FISH results.

Two areas in which the ISCN 2005 nomenclature lacksclarity and efficiency involve the introduction of (i) multi-ple choices for FISH nomenclature and (ii) a new system ofstemline and sideline nomenclature.

Although it is true that the FISH section contains well-accepted and easy ways to write FISH nomenclature, espe-cially when it comes to subtelomeric results, it is also truethat cytogeneticists are given various optionsdincludingthe choice of mentioning or not mentioning the chromo-some location targeted by a probe. (For examples, see p.111 in ISCN 2005 [2].) Allowing the use of multiple op-tions to write FISH results will lead to inconsistencies in re-ports and articles. Furthermore, these inconsistencies areexacerbated by other options given in the same FISH sec-tion. These include options to use the clone, the locus, orthe gene symbols according to the HUGO nomenclature[http://www.gene.ucl.ac.uk/nomenclature/]. These variouschoices are certain to augment the number of different waysalready used to describe identical findings.

Clinical cytogeneticists involved in CAP (Clinical Ana-tomic Pathology) proficiencies know too well how long thelist of the FISH results describing the same aberration canbe. Cytogeneticists now need considerable imagination inwriting the FISH nomenclature, geared to make up for

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the lack of examples in the 1995 ISCN version [3]. Notethat CAP proficiency testing grading considers most ofthe FISH results provided by the various clinical laborato-ries as acceptable; however, while these may be graded ac-ceptable, they also prove to be anything but standard.

The only standard component of FISH nomenclature sofar has been the name of the probe, which is simply thename of the probe as provided by the manufacturer. Thisone simplicity is lost in ISCN 2005. For example, the orig-inal probe name, TEL/AML1, is still listed as such in man-ufacturers’ catalogs. According to ISCN 2005, however, thename of this probe should be updated to ETV6/RUNX1,according to the current HUGO symbols for the genes in-volved. Further complicating the use of gene symbols inthe FISH nomenclature is the ever-changing status of for-mal gene designation. For example, AML1 first becameCBFA2 and then RUNX1dwhich is, for now, the approvedHUGO symbol.

The decision by the ISCN 2005 Standing Committee tobypass the former consistency in probe citation has addednew layers of variability, instead of providing a standardway to write the FISH nomenclature. According to ISCN2005, then, a particular FISH result can now be written us-ing the clone, the locus, or the gene symbol, with or withoutthe chromosome location targeted by the probe. Cytogenet-icists are still struggling to adopt these proposed modifica-tions, not only at the report level, but at the database levelas well.

The nomenclature for cancer cytogenetics is often chal-lenging, particularly for changes in solid tumors, due to thegreat complexity in karyotypes. This situation at one pointled to a special issue for such nomenclature, known asISCN 1991 [4], which was later incorporated (withrevisions) into ISCN 1995 [3]. The ISCN 1995 systemhas served the field well; it became the standard by whichcytogenetic results in leukemia and solid tumors arereported.

The introduction in the ISCN 2005 chapter on neoplasia(chapter 11) of two newly created terms, stemline (abbrevi-ation: ‘‘sl’’) and sideline (abbreviation: ‘‘sdl’’), may meetwith some resistance from cytogeneticists. Mitelman andRowley [5] have discussed the problems with these termi-nologies in a trenchant editorial. The ‘‘sl’’ and ‘‘sdl’’ termi-nology was introduced in ISCN 2005 as a substitute for theterm ‘‘idem’’ in describing chromosome findings with more

90 Editorial / Cancer Genetics and Cytogenetics 175 (2007) 89e90

than one subclone and was intended to eliminate the needto repeat the aberrations in each subclone.

The use of the ‘‘sl’’ and ‘‘sdl’’ terminology might savespace, but it does not appear to save time, and may im-pede understanding. It is not easy to determine at firstglance which changes are present in the first subclone inrelation to the second, third, and so on. Furthermore,and probably most critical, the ‘‘sl’’ and ‘‘sdl’’ terminol-ogy will certainly cause confusion in interpreting karyo-types containing more than one stemline (sl) and morethan one sideline (sdl) for each stemline. In this situation,each stemline has to be designated ‘‘sl’’ and each of thesubclones will be identified as sdl1, sdl2, and so on.The difficulties involved in trying to determine whichsideline belongs to which stemline have been discussedby Mitelman and Rowley [5,6].

Although the presence of multiple clones and associatedsubclones is not an everyday problem in hematologic ma-lignancies, it is frequently encountered in solid tumor cyto-genetics. This is probably one of the situations in which

a cytogeneticist has to rely again on imagination to makeup for ISCN 2005 shortcomings.

Aurelia M. Meloni-Ehrig, PhD, DScAssociate Editor

Cancer Genetics and Cytogenetics

References

[1] Tjio JH, Levan A. The chromosome number of man. Hereditas 1956;

42:1e6.

[2] ISCN 2005: an international system for human cytogenetic nomencla-

ture (2005). In: Shaffer LG, Tommerup N, editors. Basel: S. Karger, 2005.

[3] ISCN 1995: an international system for human cytogenetic nomencla-

ture (1995). In: Mitelman F, editor. Basel: S. Karger, 1995.

[4] ISCN 1991: guidelines for cancer cytogenetics. Supplement to an

International System for Human Cytogenetic Nomenclature. In:

Mitelman F, editor. Basel: S. Karger, 1991.

[5] Mitelman F, Rowley JD. ISCN (2005) is not acceptable for describing

clonal evolution in cancer [Editorial]. Genes Chromosomes Cancer

2007;46:213e4.

[6] Mitelman F, Rowley JD. Response to letter by the ISCN Standing

Committee. Genes Chromosomes Cancer 2007;46:516.