Genome-wide single nucleotide polymorphism analysis reveals frequent partial uniparental disomy due to somatic recombination in acute myeloid leukemias

• Published in: Cancer research (Chicago, Ill.) Vol. 65; no. 2; pp. 375 - 378
• Main Authors: RAGHAVAN, Manoj, LILLINGTON, Debra M, SKOULAKIS, Spyros, DEBERNARDI, Silvana, CHAPLIN, Tracy, FOOT, Nicola J, LISTER, T. Andrew, YOUNG, Bryan D
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15-01-2005
• Subjects: Acute Disease; Adult; Aged; Aged, 80 and over; Antineoplastic agents; Base Sequence; Biological and medical sciences; Diploidy; DNA Methylation; DNA, Neoplasm - genetics; Female; Genome, Human; Hematologic and hematopoietic diseases; Humans; Karyotyping; Leukemia, Myeloid - classification; Leukemia, Myeloid - genetics; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Polymorphism, Single Nucleotide; Uniparental Disomy; Recombination; Uniparental disomy; Partial; Acute; Malignant hemopathy; Single nucleotide polymorphism; Genome; Acute myelocytic leukemia
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.375.65.2

Genome-wide analysis of single nucleotide polymorphisms in 64 acute myeloid leukemias has revealed that approximately 20% exhibited large regions of homozygosity that could not be accounted for by visible chromosomal abnormalities in the karyotype. Further analysis confirmed that these patterns were due to partial uniparental disomy (UPD). Remission bone marrow was available from five patients showing UPD in their leukemias, and in all cases the homozygosity was found to be restricted to the leukemic clone. Two examples of UPD11p were shown to be of different parental origin as indicated by the methylation pattern of the H19 gene. Furthermore, a previously identified homozygous mutation in the CEBPA gene coincided with a large-scale UPD on chromosome 19. These cryptic chromosomal abnormalities, which seem to be nonrandom, have the characteristics of somatic recombination events and may define an important new subclass of leukemia.