Screening for DNA copy number aberrations in mucinous adenocarcinoma arising from the minor salivary gland: two case reports

The utility of the domestic cat as a model system for biomedical studies was constrained for many years by the absence of a comprehensive feline reference genome sequence assembly. While such a resource now exists, the cat continues to lag behind the domestic dog in terms of integration into the ‘One Health’ era of molecular medicine. Stimulated by the advances being made within the evolving field of comparative cancer genomics, we developed a microarray platform that allows rapid and sensitive detection of DNA copy number aberrations in feline tumors using comparative genomic hybridization analysis. The microarray comprises 110,456 unique oligonucleotide probes anchored at mean intervals of 22.6 kb throughout the feline reference genome sequence assembly, providing ~350-fold higher resolution than was previously possible using this technique. We demonstrate the utility of this resource through genomic profiling of a feline injection-site sarcoma case, revealing a highly disrupted profile of DNA copy number imbalance involving several key cancer-associated genes including KIT, TP53, PTEN, FAS and RB1. These findings were supported by targeted fluorescence in-situ hybridization analysis, which identified major alterations in chromosome structure, including complex intrachromosomal reorganization events typical of those seen in aggressive soft-tissue sarcomas of other species. We then characterized a second mass that was identified at a nearby site in the same patient almost 12 months later. This mass demonstrated a remarkably conserved genomic profile consistent with a recurrence of the original tumor; however the detection of subtle differences reflected evolution of the tumor over time. These findings exemplify the diverse potential of this microarray platform to incorporate domestic cat cancers into comparative and translational research efforts in molecular oncology.

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Tumor classification based on DNA copy number aberrations determined using SNP arrays

Oncology Reports ◽

10.3892/or.15.4.1057 ◽

2006 ◽

Cited By ~ 4

Author(s):

Yuhang Wang ◽

Fillia Makedon ◽

Justin Pearlman

Keyword(s):

Copy Number ◽

Tumor Classification ◽

Dna Copy Number ◽

Snp Arrays ◽

Copy Number Aberrations ◽

Dna Copy Number Aberrations

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Refining tumor-associated aneuploidy through ‘genomic recoding’ of recurrent DNA copy number aberrations in 150 canine non-Hodgkin lymphomas

Leukemia & Lymphoma ◽

10.3109/10428194.2011.559802 ◽

2011 ◽

Vol 52 (7) ◽

pp. 1321-1335 ◽

Cited By ~ 64

Author(s):

Rachael Thomas ◽

Eric L. Seiser ◽

Alison Motsinger-Reif ◽

Luke Borst ◽

Victor E. Valli ◽

...

Keyword(s):

Copy Number ◽

Dna Copy Number ◽

Copy Number Aberrations ◽

Dna Copy Number Aberrations

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Intratumor heterogeneity of DNA copy number aberrations in gastric and oesophageal adenocarcinomas.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.3_suppl.78 ◽

2015 ◽

Vol 33 (3_suppl) ◽

pp. 78-78

Author(s):

Matthew N Davies ◽

Donat Alpar ◽

Beatrice Griffiths ◽

Louise J Barber ◽

Kamil A Lipinski ◽

...

Keyword(s):

Pilot Study ◽

Copy Number ◽

Single Cells ◽

Critical Role ◽

Intratumor Heterogeneity ◽

Dna Copy Number ◽

Tumour Heterogeneity ◽

Copy Number Aberrations ◽

Dna Copy Number Aberrations ◽

Tissue Specimens

78 Background: DNA copy number aberrations (CNAs) are common in oesophageal and gastric adenocarcinomas (OGCs) and display extensive inter-tumour heterogeneity. CNA patterns define gastric cancer molecular subtypes and ERBB2 amplifications, present in a small fraction of patients with OGC, are predictive for ERBB2-targeted drug sensitivity. Together, this suggests a critical role of CNAs determining OGC tumour biology and clinical outcomes. Despite this, predictive and prognostic CNA biomarkers have not been identified for the majority of OGCs, precluding the development of effective personalized therapy approaches for these aggressive tumours. Intra-tumour heterogeneity, characterized by the presence of multiple subclones with distinct genetic profiles within an individual cancer, can hinder the accurate molecular analysis and classification of tumours. The aim of this pilot study was to assess whether chemotherapy-naïve localized OGCs display intra-tumour macroheterogeneity of CNA profiles. Methods: Tissue specimens from four tumour regions representing the macroscopic spatial extent of each of five OGCs were systematically collected after surgical resection. DNA extracted from these FFPE specimens was analysed by molecular inversion probe SNP arrays for high resolution CNA detection. Results: Comparison of genome wide copy number and B-allele frequency profiles suggested highly concordant CNA profiles across the regions from individual primary tumours. Eight driver CNAs leading to amplification of the MET, KRAS, ERBB2, PIK3CA or FGFR2 oncogenes were identified in 4/5 tumours. Only one out of these eight driver CNA’s, harbouring the KRAS oncogene, was heterogeneous within a tumour. Conclusions: Although chromosomal instability is thought to be common in this tumour type, this pilot study suggests that macroheterogeneity is limited and that CNA profiles assessed from a single tumour biopsy are likely to be representative of the dominant CNA profile of localized OGCs. Thus, clinical correlative CNA analyses may be possible from single biopsies of localized OGCs. Mutational heterogeneity and microheterogeneity in microdissected and single cells are currently being investigated.

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