title: Significance of myelodysplastic syndrome-associated somatic variants in the evaluation of patients with pancytopenia and idiopathic cytopenias of undetermined significance.
abstract: In this study, we set out to evaluate the frequency of mutations in 20 myelodysplastic syndrome-associated genes in 53 individuals with pancytopenia in which bone marrow evaluation failed to meet standard criteria for a diagnosis of myelodysplastic syndrome. These idiopathic pancytopenia cases were associated with no specific cause for their pancytopenia (n=28), aplastic anemia (n=13), pancytopenia attributable to liver disease (n=4), pancytopenia associated with autoimmune disease (n=4), and pancytopenia attributed to drug effect (n=4). We also selected 38 bone marrow aspirates from patients presenting with pancytopenia and meeting criteria for a diagnosis of myelodysplastic syndrome (n=21) or acute myeloid leukemia (n=17) as malignant comparison cases. Targeted sequencing of the 20 genes was performed on all cases. The idiopathic pancytopenia group had a lower average age (46 vs 66 years, P<0.0001) and a lower number of mutations per case that were statistically significant (0.81 vs 1.18, P=0.045). The frequency of cases with at least one mutation was higher for cases with a diagnosable myeloid neoplasm (68 vs 38%, P=0.012). Except for mutations in U2AF1, which was mutated in 5 of the 38 malignant cases (13.2%) and in none of the idiopathic pancytopenia cases (P=0.011), the frequency of mutations in the genes evaluated was not significantly different between idiopathic pancytopenia and malignant cases. Median and mean clinical follow-up for the idiopathic pancytopenia group was available for 444 and 739 days, respectively. Over this time frame, none of the idiopathic pancytopenia patients was diagnosed with a myelodysplastic syndrome or an acute myeloid leukemia. These findings provide further evidence that identification of mutations in several genes associated with myelodysplastic syndromes should not be used alone to support a diagnosis of a myelodysplastic syndrome.
authors.affiliation: Department of Pathology, Stanford University, Stanford, CA, USA.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Fernandez-Pol
authors.affiliation: Department of Pathology, Stanford University, Stanford, CA, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Pathology, Stanford University, Stanford, CA, USA.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Ohgami
authors.affiliation: Department of Pathology, Stanford University, Stanford, CA, USA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Arber
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001856:Bone Marrow Examination; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000473:pathology; D010198:Pancytopenia / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D055815:Young Adult
chemical_list: D005819:Genetic Markers