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Cancer Biomark. 2017;18(2):215-220. doi: 10.3233/CBM-161680.

ALK gene copy number in lung cancer: Unspecific polyploidy versus specific amplification visible as double minutes.

Author information

1
Department of Diagnostics and Public Health, Anatomic Pathology, University and Hospital Trust, Verona, Italy.
2
Medical Oncology, University and Hospital Trust, Verona, Italy.
3
Department of Pathology, Laboratory of Molecular Cytogenetic, University of Helsinki, Helsinki, Finland.
4
Arsenàl, Veneto's Research Center for eHealth Innovation, Veneto, Italy.
5
Anatomic Pathology, SacroCuore Hospital, Negrar, Italy.
6
Thoracic Surgery, SacroCuore Hospital, Negrar, Italy.
7
Dana-Farber Cancer Institute, Harvard Medical School, Brigham And Women's Hospital, Boston, MA, USA.
8
Anatomic Pathology, Pederzoli Hospital, Peschiera Del Garda, Verona, Italy.

Abstract

BACKGROUND:

Gains of a gene due to DNA polyploidy versus amplification of the specific locus are distinct molecular alterations in tumors.

OBJECTIVE:

We quantified copy number gains of ALK gene due to unspecific polyploidy versus amplifications of the specific locus in a series of non-small cell lung cancers.

METHODS:

The locus specific ALK copy (LSI) number status was evaluated in 205 cases by FISH. Ratio LSI ALK copy number corrected for control probes CEP2, CEP3 and CEP17 (CEPs) was scored. Amplification of the specific ALK locus was defined when ratio set to ≥ 2 while polyploidy was interpreted when the increase in gene copy resulted < 2 in ratio (LSI/control CEPs).

RESULTS:

Twenty one cases (10.2%) showed ≥ 8 ALK signals, 68 cases (33.2%) 3-7 signals and 116 cases (56.6%) a mean of 2 signals. Only 2/21 cases of the cohort harboring ≥ 8 signals showed a ratio ≥ 2 after CEPs correction interpretable as amplified, showing numerous doubled fluorescent spots. All the remaining cases showed a mirrored number of fluorescent spots per each CEPs, interpretable as polyploidy.

CONCLUSION:

We detected a high prevalence of ALK gene copy number usually due to polyploidy rather than ALK locus amplification, the latter visible prevalently as double minutes.

KEYWORDS:

ALK gene copy number; amplification; double minutes; gains; polyploidy

PMID:
28009326
DOI:
10.3233/CBM-161680
[Indexed for MEDLINE]

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