User Guide

Abnormality

• Select Yes in the Sole Abnormality field in the Cases Cytogenetics Searcher to find cases that contain this chosen abnormality and no other.
• Enter a single or multiple entries, separated by a comma.
• Click the And radio button to get results with all of the multiple entries or the Or radio button to get results with any of the multiple entries.
• Use standard wildcard characters, i.e., * matches a string of any length and _ matches a single character. All abnormality searches are automatically wildcarded on the right, but not on the left. Thus, a wildcard must be used to obtain the derivative chromosomes containing the chosen abnormality, e.g., *t(2;10)(p21;q22) will present all the der chromosomes with this translocation.
• To do an 'exact match' search for each entry, wrap the entry in double quotes, e.g. "+2".
• Use not to exclude an entry from results, e.g., +7, not +2.

Age

• Enter simple integers, e.g., 4 or 25 or ranges, e.g., 4-8 or <10.
• Use 0 to denote less than 12 months.

Authors

• Enter a single author or multiple authors, separated by a comma. Results will contain references with all authors specified.
• Use standard name format without periods after initials, e.g., Johnson H
  • Entering Mendel will match any author whose last name is Mendel, regardless of initials.
  • Entering Mendel G will match only an author whose last name is Mendel and whose only initial is G.
• Use standard wildcard characters, i.e., * matches a string of any length and _ matches a single character.
  • Entering Mendel *, with an internal space, is equivalent to entering Mendel.
  • Entering Mendel*, with no internal space, will match any author whose last name begins with Mendel, including, for example, Mendelsohn H.
• Use the single-character wildcard (_) to represent the following non-English characters in a name ( ö, å, é, ä, ü, Ö, Å, É ).

Breakpoint

• Enter a single or multiple entries, separated by a comma.
• Click the And radio button to get results with all of the multiple entries or the Or radio button to get results with any of the multiple entries.
• Use standard wildcard characters, i.e., * matches a string of any length and _ matches a single character.
  • Breakpoints have an implicit wildcard for band numbers, e.g., 1p will match any breakpoint on 1p, and 14q3 will match breakpoints on 14q31 or 14q32.
• To do an 'exact match' search for each entry, wrap the entry in double quotes, e.g. "14q3".
• Use not to exclude an entry from results, e.g., 2q21, not 2p13.

Number of Clones

• Enter simple integers, e.g., 4 or 25 or ranges, e.g., 4-8 or >10.

Number of Chromosomes

• Enter simple integers, e.g., 46 or 50 or ranges, e.g., 46-50 or <62.

Gene

• Type in the gene name to filter the inputs from the drop down list and selecting the value
• To filter the gene name:
  • Enter gene designation to find rearranged gene, e.g., BCR.
  • Enter gene designations separated by double colons :: to find gene fusions only, e.g., BCR::ABL1.
  • Use plus + before gene designation to retrieve amplifications associated with homogeneously staining regions, giant marker chromosomes, ring chromosomes, and double minutes, e.g., +MYCN.

Journal

• Use valid MEDLINE abbreviations (see List of Journal Abbreviations).
• Use standard wildcard characters, i.e., * matches a string of any length and _ matches a single character. All abnormality searches are automatically wildcarded on the right, but not on the left.
• To do an 'exact match' search for each entry, wrap the entry in double quotes, e.g. "N Engl J Med".

Morphology

• Use morphology designation followed by (all subtypes) to get all subclassified cases within entry (i.e. Acute myeloid leukemia (all subtypes) will present AML NOS and FAB types M0-M7)

Special Hereditary Disorder

• Enter a special hereditary disorder from the List of Special Hereditary Disorders.

Special Morphology

• Enter a special morphology from the List of Special Morphologies.

Year

• Enter simple integers, e.g., 1995 or range, e.g., 1992-1997 or <1996.

Abnormality

Abnormal element of a karyoptype, e.g., t(1;6)(p21;q12).

• The nomenclature for chromosomal abnormalities follows the recommendations proposed by ISCN. See ISCN Abbreviated Terms and Symbols for a brief summary and explanation of terms and symbols. The short ISCN system for designating structural chromosome abnormalities is used. Therefore, the transcription of some complex rearrangements originally described in the detailed system may give rise to some ambiguities. However, the bands involved in an aberration are always specified. Otherwise, no attempts have been made to "interpret" karyotypic changes; e.g., inferred breakpoints were not cataloged. Nor have obvious mistakes been corrected: Breakpoints localized to non-existing bands are listed as given in the original report.
• Only clonal aberrations are recorded in the database.
• Chronic myeloid leukemias with t(9;22) as the sole abnormality are not registered.

Breakpoint

Cytogenetic band location of abnormality, e.g., 1p21, as defined by ISCN.

Case No

Identification number used in database for each individual case within a reference. Multiple different tumors cytogenetically investigated in the same case are indicated by capital letters A, B, etc, following the Case Number.

Clinical Association

Provides information on associations between clinical parameters, most commonly outcome, and chromosomal changes and/or gene rearrangements resulting from chromosome aberrations. Information on Abnormality, Breakpoint and/or Gene may not always be available.

Number of Clones

Number of identical karyotype of one subset of cells from a sample. The operational definition of a clone follows the recommendation of ISCN : At least two cells with the same extra chromosome or structural aberration, or three cells with the same missing chromosome.

Country

Case origin when stated in publication; otherwise, in general the residence of corresponding author.

Gene

Provides information on rearranged protein-coding genes located in breakpoints of acquired cytogenetic aberrations.

• Molecular consequences of known neoplasia-associated chromosome changes are registered even if no cytogenetic investigation was performed.
• References to articles on quantitative gene alterations as a result of unbalanced cytogeneticaberrations are not recorded except for amplifications in homogeneously staining regions (hsr), giant marker chromosomes, ring chromosomes (r), and double minutes (dmin).
• Gene symbols are in accordance with the most recent Guidelines for Human Gene Nomenclature recommendations; hence there are no dashes, Roman numerals, or Greek letters within the gene designations.

Inv No

Number used in database for each consecutive investigation within a case or for a metastatic lesion at a different location.

• Whenever a tumor was studied at different times, the karyotypes are presented chronologically.
• From the second investigation onward, only the clones with new abnormalities are in general listed.
• It should be noted that the relevant chromosome aberration may be present in only one of several karyotypes presented for the case.

Gene Fusions

Protein-coding genes rearranged as a consequence of structural chromosome changes. References are provided to the first original publications in which the gene rearrangement was reported in a particular tumor type. Most gene fusions in the database have been identified through RNA sequencing. The chromosome abnormalities giving rise to such fusions are by default designated as translocations (t), unless shown to arise by other types of chromosome rearrangements (del, dup, ins, inv).

Morphology

Tumor histology.

• The nomenclature of tumor histology is based on the International Classification of Diseases for Oncology (ICD-O), the Systematized Nomenclature of Medicine (SNOMED), the French-American-British (FAB) proposals for the classification of acute leukemias and myelodysplastic syndromes, and the WHO Classification of Tumours of Soft Tissue and Bone.
• Tumors of the lymphoreticular system, as described according to the US National Cancer Institute Working Formulation (WF) and Kiel classification systems for non-Hodgkin's lymphomas (NHL), are converted to the REAL/WHO classification. All unspecified non-Hodgkin lymphomas are presented as Peripheral B-cell neoplasm, NOS.
• When chronic myeloproliferative disorders progress to acute myeoloid leukemia (AML), the following classification principle has been adopted: Patients with AML following, e.g. polycythemia vera, are entered under the latter diagnosis if they had not received genotoxic treatment, but as secondary AML if such treatment had been given. AML following a myelodysplastic phase is not registered as secondary.
• Rare tumor types grouped under special type, e.g. Benign mesenchymal tumor, special type, are presented in Special Morphology.

Previous Tumor

Yes indicates benign or malignant, treated or untreated neoplasm.

Recurrent aberration

Any aberration, structural or numerical, present in two or more cases of the same morphology or morphologic subentity, and, when applicable for solid tumors, topography. Hence, an identical aberration reported in two cases of AML M1 is recorded as recurrent whereas the same aberration when present in one case each of AML M1 and AML M2 will not appear as recurrent. Only well characterized abnormalities are presented, i.e., aberrations preceded by a ? or separated by or and abnormalities with breakpoints separated by - are excluded.

References

When a case has been reported in more than one publication, generally only the most recent reference is given. Therefore, a search for the original article may not yield any results. Data presented at congresses, conferences or workshops are not registered, even if abstracts were published in scientific journals.

Ref No

Unique identification number used in database for each individual reference.

Series

A case is categorized as Selected when reported because of a specific/unusual karyotypic feature; otherwise, the case is classified as Unselected.

Special Hereditary Disorder

Constitutional chromosome abnormality or Mendelian disorder, specified in Special Hereditary Disorder.

Tissue

Tissue used for cytogenetic investigation. Only neoplasms studied in direct preparations or after short-term in vitro culture are registered.

Topography

Tumor site, applicable for solid tumors, also grouped according to organ systems, e.g. Respiratory system (all sites).

Genomic Imbalances and Coordinates on the Karyotype Info Page

Karyotype Validation

Accessing the Karyotype Info Page

• the View Karyotype Details link in the Karyotype column on the Cases Cytogenetics Search Result page
• the karyotype from the Chromosome Aberration Case Info page

• Ref No, Case No, Inv No: Unique identification numbers associated with the case karyotype.
• Karyotype: The full karyotype retrieved from reference.
  • Invalid Karyotype: Reason for invalidating the karyotype.
  • Invalid Syntax Detected: List of any invalid aberrations detected in the karyotype.
  • Karyotype Used for Analysis: A karyotype that has been modified to disregard all invalid syntaxes and is used for analysis.
• Chromosome Abnormalities: Information about the genomic abnormalities of the clones and chromosomes.
  • View by Genomic Coordinates: The calculated data of the genomic imbalances in a table, also downloadable in a .csv file.
  • View in Chromosome Images: An ideogram which visualizes the data over chromosomes, downloadable in a .png or .svg file. Hovering the mouse over the colored block will display the genomic coordinates of the aberrations.

View Overall Chromosomal Imbalances

Selecting Samples for Analysis

To select samples for analysis on the Cases Cytogenetics Search Result page:

1. By default, all results are selected for the analysis.
2. To select a subset of the results, check the checkbox preceding each row that you want included.

The number of selected samples will be displayed in a circle on the button View Overall Chromosomal Imbalances.

View Overall Chromosomal Imbalances button

Clicking on the View Overall Chromosomal Imbalances button will run the analysis for the selected samples. It shows the combined frequency of genomic imbalances by the imbalance types in in each cytoband of the chromosomes.

• Imbalances are grouped into four categories:
  • 1 Extra Copy
  • >1 Extra Copy
  • Loss of 1 Copy
  • Homozygous Deletions
• All calculations are in relation to the diploid chromosome complement.

The analyzed results are shown in three different formats, each on its own tab:

• Charts: A bar chart visualizing the occurrence of the imbalances in all chromosomes. Read more at Charts: Display Options to learn about the available display options.
• Ideogram: An ideogram visualizing the frequency of the imbalances in all chromosomes.
• Data: A table displaying the calculated overall imbalances in all chromosomes.

Charts: Display Options

• Y-Axis Value: Occurrences can be displayed by the percentage, Frequency(%) or by the counts, No. of Occurrences.
• Hide Chromosomes with No Imbalances:
  • Check this box to hide charts with no genomic imbalances.
  • Checking this box will update certain checkboxes inside Imbalance Type and Chromosomes to filter the data.
  • This checkbox is checked by default.
• Imbalance Type^*: Filter the data by specific imbalance type.
• Chromosomes^*: Filter the data by chromosomes.
• Use the Update button to apply the changes to the chart, and the Clear All Filters button to unselect all checkboxes.

BigQuery and Data Analysis page

Data Browser page

Circos Plot

Copy Number

Gene Fusions