Identification of genetic disparity between primary and metastatic melanoma in human patients

Abstract

It is commonly accepted that cancer cell progression is accompanied by accumulation of genetic changes. Here we searched for copy number variations in melanoma and asked whether homozygous losses always cumulate during tumor cell progression. Therefore we investigated either melanoma cell lines or tissue derived from the primary lesion and from the lymph node metastasis of the same individual patient. In vitro studies of melanoma cell lines revealed high migratory and anchorage independent growth of metastasis-derived cells. Surprisingly, whole genome DNA analysis of a primum-derived cell line revealed a total of 10 homozygous losses, whereas the matched metastasis-derived cell line only shared five of those losses. We further tested these cells in a mouse model for intradermal melanoma growth and detected fast growth of the metastasis-derived cell line and no growth of primum-derived cells. Additionally, we screened matched pairs of patient-derived melanoma primum and metastasis samples and we could also identify a case with homozygous deletions exclusively present in the primary lesion. Therefore, we suggest that tumor cell progression at the metastatic niche can occur parallel and independently from the primary tumor. We propose that for mutation-targeted therapy genotyping should be performed not only from primary, but also from metastatic melanoma.

Tonic modulation of spinal hyperexcitability by the endocannabinoid receptor system in a rat model of osteoarthritis pain

“…Metastatic melanoma from spleen (Mel.7), skin (Mel.17), lymph node (Mel.15) and ovary (Mel.14) were isolated and cultivated as described previously 28. IGR37 and IGR39 were kindly provided by Dr. Peter Petzelbauer (Department of Dermatology, Vienna) and cultivated as described previously 29. HeLa cells and melanocytes were obtained from ATCC, and human adult low calcium high temperature keratinocytes (HaCaT) cells were obtained from DKFZ (Germany).…”

Intratumor and Intertumor Heterogeneity in Melanoma

“…It is known that the main cause of intertumor (intrapatient) heterogeneity ( Figure 1 B ) is intratumor heterogeneity ( Figure 1 A ) of the primary tumor [102] , [183] , [184] . To be precise, heterogeneity of circulating tumor cells (CTCs) or CTC clusters.…”

“…Moreover, they examined 10 corresponding primary tumors and found that 5 (50%) patients exhibited additional LOH in metastases. Furthermore, Swoboda et al [184] found deletions exclusively in the primary melanoma cell line or in the matched metastatic melanoma cell line.…”

Radioiodine Therapy in Differentiated Thyroid Cancer: The First Targeted Therapy in Oncology

“…Several studies have reported alterations in gene expression and phenotypic heterogeneity between metastatic and primary cancer sites [ 21 ]. The heterogeneity is primarily caused by differences in gene expression at different metastatic sites.…”