The coincidence of chromosome 15 aberrations and β2-microglobulin gene mutations is causative for the total loss of human leukocyte antigen class I expression in melanoma

• Verfasst von: Paschen, Annette [VerfasserIn]
• Verfasst von: Sucker, Antje [VerfasserIn]
• Verfasst von: Greulich-Bode, Karin Maria [VerfasserIn]
• Verfasst von: Striegel, Sandra [VerfasserIn]
• Verfasst von: Schwinn, Nicole [VerfasserIn]
• Verfasst von: Hildenbrand, Ralf [VerfasserIn]
• Verfasst von: Cerwenka, Adelheid [VerfasserIn]
• Verfasst von: Schadendorf, Dirk [VerfasserIn]
• Titel: The coincidence of chromosome 15 aberrations and β2-microglobulin gene mutations is causative for the total loss of human leukocyte antigen class I expression in melanoma
• Verf.angabe: Annette Paschen, Norbert Arens, Antje Sucker, Karin M. Greulich-Bode, Ester Fonsatti, Annunziata Gloghini, Sandra Striegel, Nicole Schwinn, Antonino Carbone, Ralf Hildenbrand, Adelheid Cerwenka, Michele Maio, and Dirk Schadendorf
• E-Jahr: 2006
• Jahr: June 1, 2006
• Umfang: 9 S.
• Fussnoten: Gesehen am 09.02.2021
• Titel Quelle: Enthalten in: Clinical cancer research
• Ort Quelle: Philadelphia, Pa. [u.a.] : AACR, 1995
• Jahr Quelle: 2006
• Band/Heft Quelle: 12(2006), 11, Seite 3297-3305
• ISSN Quelle: 1557-3265
• DOI: doi:10.1158/1078-0432.CCR-05-2174
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1747885606

Abstract

Purpose: Total loss of surface presentation of human leukocyte antigen (HLA) class I molecules, protecting tumor cells from the recognition by cytotoxic host CD8+ T cells, is known to be caused by mutations in the β2-microglobulin (β2m) gene. We asked whether abnormalities of chromosome 15, harboring the β2m gene on 15q21, in addition to β2m gene mutations, are causative for the HLA class I-negative phenotype of melanoma cells. - Experimental Design: To answer this, we established primary cell lines from the β2m-negative metastatic melanoma tissues of four different patients and analyzed them for β2m gene mutations and chromosome 15 aberrations, the latter by loss of heterozygosity analysis, fluorescence in situ hybridization (FISH), and multicolor FISH. - Results: Mutations at the β2m gene level were detected in all cell lines. The loss of heterozygosity analysis of microsatellite markers located on chromosome 15 in three of the four cell lines pointed to an extensive loss of chromosome 15 material. Subsequent molecular cytogenetic analysis revealed the coexistence of apparently normal and rearranged versions of chromosome 15 in three cell lines whereas the fourth cell line solely showed rearranged versions. Two of the four cell lines exhibited a special type of intrachromosomal rearrangement characterized by FISH signals specific for the subtelomeric region of 15q at both ends of the chromosome and one centromeric signal in between. - Conclusions: Our data indicate that the complete loss of HLA class I expression in melanoma cells is due to the coincidence of the following mutational events: (a) chromosome 15 instability associated with an extensive loss of genetic material and (b) β2m gene mutations.