De novo deletion 17p13.1 as a predictor for disease progression in chronic lymphocytic leukemia

El-Ghammaz, Amro Mohamed Sedky; Abdelwahed, Essam; Mostafa, Nevine N; Mansour, Dina

doi:10.1007/s10238-014-0317-2

Cited by 3 publications

(3 citation statements)

References 31 publications

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“…The most common TP53 configuration involves a missense mutation together with a segmental 17p deletion, although a substantial fraction of p53-altered tumours harboured chromosome 17p deletion together with an apparently wild-type TP53 allele. Similar results were observed in blood cancers, in which TP53 mutations and/or 17p loss are less common but are linked to a particularly dismal prognosis 9,10 . Hence, the frequency of 17p deletion may even exceed point mutations within the TP53 gene.…”

Section: Chromosome 17p Configurations In Human Cancersupporting

confidence: 81%

Deletions linked to TP53 loss drive cancer through p53-independent mechanisms

Liu

Chen

et al. 2016

Nature

228

202

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Mutations disabling the TP53 tumour suppressor gene represent the most frequent events in human cancer and typically occur through a two-hit mechanism involving a missense mutation in one allele and a ‘loss of heterozygosity’ deletion encompassing the other. While TP53 missense mutations can also contribute gain-of-function activities that impact tumour progression, it remains unclear whether the deletion event, which frequently includes many genes, impacts tumorigenesis beyond TP53 loss alone. Here we show that somatic heterozygous deletion of mouse chromosome 11B3, a 4-megabase region syntenic to human 17p13.1, produces a greater effect on lymphoma and leukaemia development than Trp53 deletion. Mechanistically, the effect of 11B3 loss on tumorigenesis involves co-deleted genes such as Eif5a and Alox15b (also known as Alox8), the suppression of which cooperates with Trp53 loss to produce more aggressive disease. Our results imply that the selective advantage produced by human chromosome 17p deletion reflects the combined impact of TP53 loss and the reduced dosage of linked tumour suppressor genes.

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Section: Chromosome 17p Configurations In Human Cancersupporting

confidence: 81%

Deletions linked to TP53 loss drive cancer through p53-independent mechanisms

Liu

Chen

et al. 2016

Nature

228

202

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“…S1A), although loss of heterozygosity (LOH) in the region of chromosome 17p that harbors the EIF5A and/or TP53 genes is frequent in many tumors (refs. 27–29 ; Fig. 1B , shallow deletion −1: orange).…”

Section: Resultsmentioning

confidence: 98%

The Polyamine–Hypusine Circuit Controls an Oncogenic Translational Program Essential for Malignant Conversion in MYC-Driven Lymphoma

Nakanishi

Berglund

et al. 2023

Blood Cancer Discovery

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The MYC oncoprotein is activated in a broad spectrum of human malignancies and transcriptionally reprograms the genome to drive cancer cell growth. Given this, it is unclear if targeting a single effector of MYC will have therapeutic benefit. MYC activates the polyamine-hypusine circuit, which post-translationally modifies the eukaryotic translation factor eIF5A. The roles of this circuit in cancer are unclear. Here we report essential intrinsic roles for hypusinated eIF5A in the development and maintenance of MYC-driven lymphoma, where loss of eIF5A hypusination abolishes malignant transformation of MYC-overexpressing B cells. Mechanistically, integrating RNA-seq, Ribo-seq and proteomic analyses revealed that efficient translation of select targets is dependent upon eIF5A hypusination, including regulators of G1-to-S phase cell cycle progression and DNA replication. This circuit thus controls MYC’s proliferative response, and it is also activated across multiple malignancies. These findings suggest the hypusine circuit as a therapeutic target for several human tumor types.

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“…Вработах [9,10]такжебылопоказано,чтоучастипа-циентовсdel17p13болезньможетпротекатьбессимп-томновтечениедлительногопериода.Авторысделали вывод,чтопотеря17p13являетсяпредикторомтолько прогрессиррованиязаболевания,ноневыживаемости больных.…”

Section: делеция 17p13unclassified