Trisomy 14 as a Sole Chromosome Abnormality Is Associated with Older Age, a Heterogenous Group of Myeloid Neoplasms with Dysplasia, and a Wide Spectrum of Disease Progression

Abstract

Trisomy 14 is a rare recurrent cytogenetic abnormality in myeloid neoplasms; however, its clinicopathologic features have not been well described. We report the clinicopathologic, immunophenotypic, and molecular genetic features of 16 cases of myeloid neoplasms with isolated trisomy 14. Our results show that cases with isolated trisomy 14 encompass a heterogenous group of myeloid neoplasms including myelodysplastic syndrome (MDS, 44%), myelodysplastic/myeloproliferative neoplasms (31%), and acute myeloid leukemia (25%). The patients are usually elder (median age 71 years), and there is a male predominance (82%). Multilineage dysplasia is noted in all cases. Oncogenic mutations of genes involved in cell proliferation and/or survival rarely occur. Compared with cases of MDS with diploid karyotype, patients of MDS with isolated trisomy 14 demonstrate a similar overall survival and rate of leukemia transformation.

Germline duplication of ATG2B and GSKIP predisposes to familial myeloid malignancies

“…The 700-kb germline duplicated region identified here, which segregates among the 24 affected family members of the 4 families, is associated with a high penetrance level, above 80%. The predisposition locus is located in the 14q32.2 region, which is rarely affected by recurrent cytogenetic aberrations in chronic and acute phases of MPN evolution [25][26][27] , although trisomy 14 has been associated with myeloid malignancies that develop in older individuals 28,29 , in MDS, atypical chronic myeloid leukemia (aCML) and CMML 30,31 . Interestingly, one patient (F1:II-7) who directly developed an acute leukemia demonstrated mosaic trisomy 14 with up to five copies of the CNV, arguing for a gene dosage effect.…”

Acute myeloid leucaemia with trisomy 14 as a sole cytogenetic abnormality

“…Few cases of isolated trisomy 14 in myeloid neoplasms have been reported in the literature, with most observed in myelodysplastic syndromes 1. Given its normal erythroid and megarkaryocytic maturation, we posit that the present case arose as a de novo AML, which has not been previously reported.…”

Next‐generation sequencing reveals unique combination of mutations in cis of CSF3R in atypical chronic myeloid leukemia

“…In addition, sole trisomy 14 was found in chromosome analysis. The chromosomal aberration is also reported to be related with dysplastic blood cancer, while further investigation is needed for its biology and clinical significance …”

“…Chromosome analysis showed 47,XX,+14 [19]/46,XX [1]. Molecular genetic studies were performed to screen BCR/ABL1, PDGFRA, PDGFRB, and FGFR1 rearrangements, and point mutations of JAK2, CALR, and MPL, and the results were all negative.…”