Bloom syndrome and the underlying causes of genetic instability

Ababou, Mouna

doi:10.1016/j.ymgme.2021.03.003

Cited by 35 publications

(36 citation statements)

References 218 publications

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“…Among these 28 P-proteins, we focused on the Bloom syndrome protein (BLM) as a putative SMYD3 interactor ( Appendix Table S3 ) because of its involvement in cancer. Together with other RECq helicase family members, BLM is considered a tumor suppressor that finely regulates chromosomal stability at the telomeric and centromeric level during critical phases (DNA crosslink and DNA replication fork arrest) of DNA replication [62] , [63] . Based on our in silico analysis, BLM is the Telomere Maintenance cluster member containing the highest number of different P-tripeptides (P2 at aa position 88, P1 at aa position 192, P18 at aa position 667, and P7 at aa position 1239), one of which (P7) is located in the helicase and RNaseD C-terminal (HRDC) domain ( Appendix Table S3 ).…”

Section: Resultsmentioning

confidence: 99%

Identifying novel SMYD3 interactors on the trail of cancer hallmarks

Fasano

Signorile

Marco

et al. 2022

Computational and Structural Biotechnology Journal

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Section: Resultsmentioning

confidence: 99%

Identifying novel SMYD3 interactors on the trail of cancer hallmarks

Fasano

Signorile

Marco

et al. 2022

Computational and Structural Biotechnology Journal

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“…BLM and FANCI play an essential role in homologous recombination (HR)-mediated repair of DNA interstrand cross-links, the mutation of which resulted in the deficiency of DNA repair and lead to genome instability (68). The biallelic germline mutations of BLM and FANCI resulted in Bloom syndrome and Fanconi anemia (FA), respectively, characterized by congenital disabilities and cancer predisposition (69,70). Recently, several studies have also revealed the gene-dose effect (haploinsufficiency) of BLM and FA family genes may be associated with cancer predisposition (71)(72)(73).…”

Section: Investigation Of Similarities Between Synchronous Sbl and Hbmentioning

confidence: 99%

The Cellular and Molecular Landscape of Synchronous Pediatric Sialoblastoma and Hepatoblastoma

Yang

Zhan

et al. 2022

Front. Oncol.

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Sialoblastoma (SBL) is an infrequent embryonal malignant tumor originating from the salivary gland, resembling primitive salivary gland anlage, whereas hepatoblastoma (HB) is the most common pediatric liver malignancy. The simultaneous occurrence of both tumors is extremely rare. Here we reported a case of a 6-month-old infant diagnosed with synchronous SBL and HB. The patient received neoadjuvant chemotherapy followed by surgical resection. Fresh tissues of both tumors were collected before and after chemotherapy, which were further profiled by whole exome sequencing (WES) and single-cell RNA sequencing (scRNA-seq). WES analysis revealed potential somatic driver mutation PIK3CA p.Glu454Lys for SBL and canonical mutation CTNNB1 p.Ser45Pro for HB. No shared somatic variants or common copy number alterations were found between SBL and HB primary tumor samples. Though scRNA-seq, single-cell atlases were constructed for both tumors. SBL may recapitulate a pre-acinar stage in the development of salivary gland, including basaloid, duct-like, myoepithelial-like, and cycling phenotypes. In the meantime, HB was composed of tumor cells resembling different stages of the liver, including hepatocyte-like, hepatic progenitor-like, and hepatoblast-like cells. After chemotherapy, both tumors were induced into a more mature phenotype. In terms of transcriptional signatures, SBL and HB showed enhanced expression of epithelial markers KRT8, KRT18, and essential embryo development genes SDC1, MDK, indicating the disruption of normal embryo epithelium development. Finally, heterozygous deleterious germline mutation BLM and FANCI were identified which could predispose the patient to higher cancer risk. It partially explained the reason for the co-occurrence of SBL and HB. Taken together, we provided valuable resources for deciphering cellular heterogeneity and adaptive change of tumor cells after chemotherapy for synchronous SBL and HB, providing insights into the mechanisms leading to synchronous pediatric tumors.

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“…Chromosomes in cells from patients with BSyn display increased frequency of sister chromatid exchanges secondary to the role of BLM in homologous recombination described above. This is thought to be the underlying mechanism for their increased risk of cancer ( Ababou, 2021 ). They develop a wide spectrum of cancer types, with hematologic and gastrointestinal malignancies being most frequent, at younger ages than the general population.…”

Section: Overview Of Dna Recq Helicases In Cancermentioning

confidence: 99%

RecQ Helicase Somatic Alterations in Cancer

Thakkar

Lee²,

Meyer³

et al. 2022

Front. Mol. Biosci.

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Named the “caretakers” of the genome, RecQ helicases function in several pathways to maintain genomic stability and repair DNA. This highly conserved family of enzymes consist of five different proteins in humans: RECQL1, BLM, WRN, RECQL4, and RECQL5. Biallelic germline mutations in BLM, WRN, and RECQL4 have been linked to rare cancer-predisposing syndromes. Emerging research has also implicated somatic alterations in RecQ helicases in a variety of cancers, including hematological malignancies, breast cancer, osteosarcoma, amongst others. These alterations in RecQ helicases, particularly overexpression, may lead to increased resistance of cancer cells to conventional chemotherapy. Downregulation of these proteins may allow for increased sensitivity to chemotherapy, and, therefore, may be important therapeutic targets. Here we provide a comprehensive review of our current understanding of the role of RecQ DNA helicases in cancer and discuss the potential therapeutic opportunities in targeting these helicases.

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Bloom syndrome and the underlying causes of genetic instability

Cited by 35 publications

References 218 publications

Identifying novel SMYD3 interactors on the trail of cancer hallmarks

Identifying novel SMYD3 interactors on the trail of cancer hallmarks

The Cellular and Molecular Landscape of Synchronous Pediatric Sialoblastoma and Hepatoblastoma

RecQ Helicase Somatic Alterations in Cancer

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