PhD Scientific Days 2017

Poster Presentation: Oncology

P43: Organ-specific CNV patterns of distant metastatic melanomas revealed by aCGH

Előadó neve

Papp, Orsolya

Előadó munkahelye

2nd Department of Pathology

Előadó telefonszáma

+36303253435

Előadó e-mail címe

papporsolya91@gmail.com

Az előadás címe

Organ-specific CNV patterns of distant metastatic melanomas revealed by aCGH

Szerző(k) neve és munkahelye

Orsolya Papp1, Laura Vízkeleti1,2, Viktória Doma1, Lilla Reiniger2,3, Attila Kovács1, Violetta Piurkó1, József Tímár1,4
1 2nd Department of Pathology, Semmelweis University, Budapest, Hungary.
2 MTA-SE-NAP B Brain Metastasis Research Group
3 1st Department of Pathology, Semmelweis University, Budapest, Hungary.
4 MTA-SE Tumor Progression Research Group, Budapest, Hungary.

Szekció

Poster Presentation: Oncology

Data of the presenter

Doctoral School: Pathological Sciences, Oncology program
Supervisor: József Tímár
e-mail: papporsolya91@gmail.com

Text of the abstract

Introduction: Distant metastatic process is the predominant cause of melanoma specific death. Despite intensive research, there is still no effective therapy for patients with advanced staged disease.
Aims: Our primary goal was to determine alterations in CNV pattern of cutaneous melanomas with different oncogenic driver mutations (NRAS, BRAF or double wild type) and matched distant metastases (brain, lung and liver).
Methods: Affymetrix OncoScan and CytoScan HD platforms were used to analyze CNV patterns. Raw data analysis was performed with Nexus Copy Number 8.0 and ChAs softwares. Pathway analysis was established by web-accessed DAVID 6.8 database.
Results: Increased number of genomic alteration was observed in distant metastases (DM) compared to primary tumors (average 21.7% vs. 14.3%). Generally, CN gain of genes involved in cell adhesion and motility pathways was observed in DMs. Comparing CNV patterns of different DM sites, brain showed higher copy of defensine genes. Liver metastases were characterized by amplification of scramblases, genes in Ca- and cadherin dependent cell adhesion and WNT signaling, and loss of protein phosphatase and metallopeptidase coding genes. Lung metastases were featured by overrepresentation of genes in transcription regulation (e.g. histone modification), cell cycle and TNF pathways, whereas CN loss was observed in metiltransferase activity and spectrin associated microfilament development. Based on the ongoing analysis of differences between distinct molecular subtypes, NRAS mutated primary and metastatic tumors show a different CNV pattern with overall a high percentage of altered genome.
Conclusion: In concert with literature, our results revealed increasing chromosomal instability during metastatic process. Moreover, differently altered pathways in distinct organ metastases bearing different driver mutations suggest that metastatic process is not uniform, and should depend on the microenvironment of host organ. This may have future consequences in management of advanced disease.

Azonosító

P43

Kind

Szabad

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

1259

Authors (legacy)

Orsolya Papp1, Laura Vízkeleti1,2, Viktória Doma1, Lilla Reiniger2,3, Attila Kovács1, Violetta Piurkó1, József Tímár1,4
1 2nd Department of Pathology, Semmelweis University, Budapest, Hungary.
2 MTA-SE-NAP B Brain Metastasis Research Group
3 1st Department of Pathology, Semmelweis University, Budapest, Hungary.
4 MTA-SE Tumor Progression Research Group, Budapest, Hungary.