Exome sequencing reveals recurrent germ line variants in patients with familial Waldenström macroglobulinemia

Roccaro, Aldo M.; Sacco, Antonio; Shi, Jiantao; Chiarini, Marco; Perilla-Glen, Adriana; Manier, Salomon; Glavey, Siobhán; Aljawai, Yosra; Mishima, Yuji; Kawano, Yawara; Moschetta, Michele; Correll, Mick; Improgo, Ma. Reina D.; Brown, Jennifer R.; Rossi, Giuseppe; Castillo, Jorge J.; Treon, Steven P.; Freedman, Matthew L.; Allen, Eliezer M. Van; Hide, Winston; Hiller, Elaine; Rainville, Irene; Ghobrial, Irène M.

doi:10.1182/blood-2015-11-680199

Cited by 23 publications

(6 citation statements)

References 48 publications

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“…Nearly 30 novel susceptibility genes have been identified using various forms of DNA sequencing in the last five years. Some of these novel genes are listed in Table 2 18–24 while others were summarized in a previous review 25 . Examples include variants in the POLE gene in colorectal cancer 26 or variants in the promoter region of TERT in familial and sporadic melanoma 27 .…”

Section: Novel Genomic Approaches To Cancer Preventionmentioning

confidence: 99%

Genomic approaches to accelerate cancer interception

Beane

Campbell

Lel

et al. 2017

The Lancet Oncology

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Summary While the last decade has witnessed major advances in the treatment of late stage cancers with targeted and immune-based therapies, there is a critical unmet need to develop new approaches to impact the prevention and early detection of cancer. Recent advances in the field of genomics and computational biology offer unprecedented opportunities to understand the earliest molecular events associated with carcinogenesis, leading to novel strategies to intercept the development of invasive cancers. This review will highlight emerging “big data” genomic approaches that have the potential to accelerate advances in cancer prevention, screening and early detection across a variety of tumor types along with the challenges inherent in developing these tools for use in the clinic. Through coordinated multicenter consortia, these genomic approaches promise to transform the landscape of cancer interception in the coming years.

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Section: Novel Genomic Approaches To Cancer Preventionmentioning

confidence: 99%

Genomic approaches to accelerate cancer interception

Beane

Campbell

Lel

et al. 2017

The Lancet Oncology

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“…Authors have also demonstrated the 100% occurrence of the variant in WM patients with family history, [20] findings also confirmed more recently in a separate series of studies reporting on the role of LAPTM5 and HCLS1 germline variants in WM patients with coinheritance for WM. [24] From a clinical point of view, patients who were homozygous for MYD88 L265P presented with a longer mean interval since the diagnosis of WM was made; no differences in terms of other clinical features and laboratory findings were observed between homozygosity and heterozygosity for this variant. [25] Authors have also characterized the functional role of this mutation and described how the MYD88 L265P variant confers WM cell proliferative advantage through NFκB (NFκB) activation (Figure 1A).…”

Section: Mutational Profiling In Wm Cells and Related Functional Sequmentioning

confidence: 99%

The importance of the genomic landscape in Waldenström's Macroglobulinemia for targeted therapeutical interventions

et al. 2017

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The Literature has recently reported on the importance of genomics in the field of hematologic malignancies, including B-cell lymphoproliferative disorders such as Waldenström's Macrolgobulinemia (WM). Particularly, whole exome sequencing has led to the identification of the MYD88L265P and CXCR4C1013G somatic variants in WM, occurring in about 90% and 30% of the patients, respectively. Subsequently, functional studies have demonstrated their functional role in supporting WM pathogenesis and disease progression, both in vitro and in vivo, thus providing the pre-clinical evidences for extremely attractive targets for novel therapeutic interventions in WM. Of note, recent evidences have also approached and defined the transcriptome profiling of WM cells, revealing a signature that mirrors the somatic aberrations demonstrated within the tumor clone. A parallel research field has also reported on microRNAs (miRNAs), highlighting the oncogenic role of miRNA-155 in WM. In the present review, we focus on the latest reports on genomics and miRNAs in WM, providing an overview of the clinical relevance of the latest acquired knowledge about genomics and miRNA aberrations in WM.

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“…There have been other reports of germ line mutations of genes causing a predisposition to leukemia that have not been replicated or reported in additional kindreds. These include the duplication of ATG2B and GSKIP, which seems to predispose to MPNs 49 ; mutations in RBB6 associated with MPNs 50 ; mutations in ACD that cause a BMF syndrome 51 ; mutations in SRP72 that lead to MDS 52 ; mutations in LAPTM5 and HCLS1 that are associated with familial Waldenström macroglobulinemia 53 ; and mutations in SH2B3 that appear to predispose to ALL. 54 Subsequent work will determine the extent to which germ line mutations in these genes have implications outside of the reported families.…”

Section: Emerging Leukemia Predisposition Syndromesmentioning

confidence: 99%

Germ line mutations associated with leukemias

Porter

2016

Hematology

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Several genetic syndromes have long been associated with a predisposition to the development of leukemia, including bone marrow failure syndromes, Down syndrome, and Li Fraumeni syndrome. Recent work has better defined the leukemia risk and outcomes in these syndromes. Also, in the last several years, a number of other germ line mutations have been discovered to define new leukemia predisposition syndromes, including ANKRD26, GATA2, PAX5, ETV6, and DDX41 In addition, data suggest that a substantial proportion of patients with therapy related leukemias harbor germ line mutations in DNA damage response genes such as BRCA1/2 and TP53 Recognition of clinical associations, acquisition of a thorough family history, and high index-of-suspicion are critical in the diagnosis of these leukemia predisposition syndromes. Accurate identification of patients with germ line mutations associated with leukemia can have important clinical implications as it relates to management of the leukemia, as well as genetic counseling of family members.

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Exome sequencing reveals recurrent germ line variants in patients with familial Waldenström macroglobulinemia

Cited by 23 publications

References 48 publications

Genomic approaches to accelerate cancer interception

Genomic approaches to accelerate cancer interception

The importance of the genomic landscape in Waldenström's Macroglobulinemia for targeted therapeutical interventions

Germ line mutations associated with leukemias

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