Loss of heterozygosity in the Hodgkin-Reed Sternberg cell line L1236

Abstract

Summary Hodgkin-Reed Sternberg cells are derived from germinal centre B-cells in most cases. Somatic mutations affecting their rearranged immunoglobulin genes were detected, rendering potential functional rearrangements non-functional. Under physiological conditions such cells would be designated to undergo apoptosis within the germinal centre. In search for the specific transforming event that prevents Hodgkin-Reed Sternberg cells from programmed cell death, cytogenetic analyses were broadly performed but did not reveal specific chromosomal aberrations. Analysis of these cells on the molecular level is difficult to perform due to the scarcity of the cells in the lymphoma tissue and the given limitations of in situ studies. To overcome these limitations, the cell line L1236, known to be derived from Hodgkin-Reed Sternberg cells in situ, was chosen for allelotype analysis. Using a panel of microsatellite loci assigned to nearly all chromosomal arms, regions of loss of heterozygosity were detected on chromosomal arms 6p, 9q and 17p. The size of lost segments was estimated by amplification of additional microsatellite loci mapped to the respective regions. Further analyses of single Hodgkin-Reed Sternberg cells will reveal whether LOH affecting these regions is a recurrent event in HD and to which extent the smallest commonly affected region can be estimated.

Non-invasive prenatal test identifies circulating cell-free DNA chromosomal abnormalities derived from clonal hematopoiesis in aggressive hematological malignancies

“…In cancers, 6p copy number neutral (CN) LOH is a very common mechanism of immune surveillance escaping, as lost of 6p arm determines the lack of expression of HLA class I alleles on cell surface, thus favoring the escape of cells from autologous attack of cytotoxic T cells [ 40 – 43 ]. Hodgkin and Reed-Stenberg cells in HL can also frequently use this mechanism to evade immune surveillance [ 44 ]. In our study, using NIPT-based technologies for liquid biopsy analysis, we demonstrated that whole chromosome 6 loss or 6p LOH are common alterations in hematological malignancies, not only in those with an immune-mediated pathogenesis, such as acquired bone marrow failure syndromes and HL.…”

“…In our study, using NIPT-based technologies for liquid biopsy analysis, we demonstrated that whole chromosome 6 loss or 6p LOH are common alterations in hematological malignancies, not only in those with an immune-mediated pathogenesis, such as acquired bone marrow failure syndromes and HL. Moreover, losses of the long arm of chromosome 6 are frequently in solid tumors, including melanoma, renal cell carcinoma, salivary gland adenocarcinoma, or ovarian carcinoma, and in hematologic malignancies, such as acute lymphoblastic leukemia and B-cell lymphomas, occurring in at least 32 and 7% of patients, respectively [ 44 ]. Among B-cell lymphomas, deletions of 6q are commonly observed in CLL, MM, DLBCL, and FL, in which are associated with adverse clinical outcomes [ 41 ].…”

Frequent hypermethylation of DBC1 in malignant lymphoproliferative neoplasms

“…Loss of heterozygosity (LOH) at the long arm of chromosome 9 has been demonstrated in several types of lymphoid malignancies, including diffuse large B-cell lymphoma, 1-3 follicular lymphoma, 4 multiple myeloma, 5 mantle cell lymphoma, 6 Hodgkin lymphoma, 7 acute lymphoblastic leukemia, 8,9 and chronic lymphocytic leukemia. 10 Some of these studies have implicated the 9q32-33 region as the prevailing target for deletion, suggesting that this region harbors an important tumor suppressor gene for lymphoproliferative cancers.…”