Detectable clonal mosaicism in blood as a biomarker of cancer risk in Fanconi anemia

Abstract

Key Points• Fanconi anemia patients have exacerbated cytogenetic clonal mosaicism as detected by molecular karyotyping of blood DNA with SNP assays.• Bone marrow clonal abnormalities can be detected in blood DNA and used as biomarkers of cancer risk and poor prognosis.Detectable clonal mosaicism for large chromosomal events has been associated with aging and an increased risk of hematological and some solid cancers. We hypothesized that genetic cancer predisposition disorders, such as Fanconi anemia (FA), could manifest a high rate of chromosomal mosaic events (CMEs) in peripheral blood, which could be used as early biomarkers of cancer risk. We studied the prevalence of CMEs by single-nucleotide polymorphism ( ). Therefore, our data suggest that molecular karyotyping with SNP arrays in easy-to-obtain blood samples could be used for better monitoring of bone marrow clonal events, cancer risk, and overall survival of FA patients.

Quantitative analysis of somatically acquired and constitutive uniparental disomy in gastrointestinal cancers

“…This finding is in agreement with previously published data suggesting that large structural genetic mosaicism was associated with aging and various types of solid tumors . In fact, chromosomal mosaic events have been recently described in patients with cancer predisposing disorders, such as Fanconi anemia . Here, we show a possible relationship between clonal mosaicism and CRC.…”

“…6,56,57 In fact, chromosomal mosaic events have been recently described in patients with cancer predisposing disorders, such as Fanconi anemia. 58 Here, we show a possible relationship between clonal mosaicism and CRC. Using the EPICOLON cohort, we identified mosaic UPD in CRC patients affecting genomic regions 5q14.3-q23.1, 11p15.5-p15.1, 17p13.3-p11.2 with known CRCrelated genes such as APC, IGF2 and TP53, respectively, and a copy number loss at 13q14.2-q14.3 involving the putative TSGs DLEU7, DLEU1, DLEU2 and the microRNAs mir-15a and miR-16-1, implicated in B-cell chronic lymphocytic leukemia.…”

Chromosomal Aberrations and Survival after Unrelated Donor Hematopoietic Stem Cell Transplant in Patients with Fanconi Anemia

“…4,5,17 However, the frequency of affected patients is higher in our study (22%) than in a previous report based on a SNP-array analysis in blood samples (12%). 17 The higher frequency in our study may be explained, at least in part, by the over-representation of patients with severe disease, since blood samples were collected during the preparation for HCT.…”

“…4,5,17 However, the frequency of affected patients is higher in our study (22%) than in a previous report based on a SNP-array analysis in blood samples (12%). 17 The higher frequency in our study may be explained, at least in part, by the over-representation of patients with severe disease, since blood samples were collected during the preparation for HCT. In the current study, the coexistence of multiple chromosomal abnormalities was not rare (9.6% of the patients had aberrations in ≥3 chromosomes, and 5/6 patients with chr3q+ had another aberration); this was also higher than observed in the previously referenced study (6/130; 4.6%).…”

“…In the current study, the coexistence of multiple chromosomal abnormalities was not rare (9.6% of the patients had aberrations in ≥3 chromosomes, and 5/6 patients with chr3q+ had another aberration); this was also higher than observed in the previously referenced study (6/130; 4.6%). 17 The cross-sectional nature of our study did not allow observation of the sequence of the occurrence of these aberrations. A previous study with follow-up molecular cytogenetic data showed that chr3q+ preceded monosomy 7 in 33% of the patients (6 out of 18); suggesting that chr3q+ may stimulate subsequent clonal aberrations in FA.…”