Editors' ChoiceCancer

Maternal Origins of Cancer Transmission

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Science Translational Medicine  18 Nov 2009:
Vol. 1, Issue 7, pp. 7ec26
DOI: 10.1126/scitranslmed.3000609

Chromosomal translocations can often give rise to new, fused genes, formed by breakage and reannealing of two previously separated chromosomal sequences. These sequences on either side of the healed breakpoint can be a unique, stable clonal marker capable of identifying the single-cell origins of a cancer. Using the leukemia fusion gene BCR-ABL1 as this sort of marker for an acute lymphocytic leukemia (ALL)/lymphoma, Isoda et al. document the transmission of a cancer clone from a 28-year-old Japanese mother to her newborn infant, who after having experienced an uncomplicated pregnancy and normal birth was subsequently diagnosed with ALL. The infant, at 11 months, presented symptomatically with a tumor mass in her cheek and a pleural effusion of the lung. Immunophenotyping and genotyping confirmed that the leukemic cells were identical to those of the mother. Furthermore, DNA obtained from the newborn's pleural effusion and DNA obtained from the mother’s bone marrow revealed identical fusion sequences at the breakpoint region—from the first intron in BCR and the first intron of ABL1. The authors further examined how these cancerous maternal cells were able to survive in the presence of the newborn’s immune system. The tumor cells in the newborn were found to have selectively deleted the HLA alleles, a group of genes that encode proteins that are required to reject foreign antigens. Loss of heterozygosity analysis of these tumor cells in the newborn show that, along with several oncogenic deletions, the whole HLA locus at chromosome 6p was lost and accompanied by duplication of the other parental 6p region. The authors conclude that this loss of HLA likely accounts for the fact that these maternally transmitted cancer cells were perceived by the newborn to be immunologically inert, allowing their survival in her system.

T. Isoda et al., Immunologically silent cancer clone transmission from mother to offspring. Proc. Nat. Acad. Sci. U.S.A. 20 October 2009 (10.1073/pnas.0904658106) [Abstract]

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