Advances in Genome Science

Volume: 2

Probing Intracellular Regulation

Indexed in: EMBASE, EBSCO.

Genome science or genomics is essential to advancing knowledge in the fields of biology and medicine. Specifically, researchers learn about the molecular biology behind genetic expression in living ...
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Cancer Proneness in Nijmegen Breakage Syndrome Carriers

Pp. 101-119 (19)

Alessandra di Masi, Francesco Berardinelli, Domenica Cilli and Antonio Antoccia

Abstract

Biallelic mutations in the NBN gene are responsible for the Nijmegen breakage syndrome (NBS), a rare autosomal recessive disorder characterized by chromosome instability and hypersensitivity to ionising radiation (IR). Epidemiological data evidence that the NBN gene can be considered a susceptibility factor for cancer development, as demonstrated by the fact that almost 40% of NBS patients have developed a malignancy before the age of 21. Interestingly, also NBN heterozygotes, which are clinically asymptomatic, display an elevated risk to develop some types of malignant tumours, especially breast, prostate and colorectal cancers, lymphoblastic leukaemia, and non-Hodgkin’s lymphoma (NHL). So far, nine mutations in the NBN gene have been found, at the heterozygous state, in cancer patients. Among them, the 657del5, the I171V and the R215W mutations are the most frequently described. The pathogenicity of these mutations is presumably connected with their occurrence in the highly conserved BRCT tandem domains of the NBN protein, which are present in a large superfamily of proteins and are recognized as major mediators of processes related to cell-cycle checkpoints and DNA repair. This review will focus on the current stateof- knowledge regarding the correlation between carriers of NBN gene mutations and the proneness to the development of malignant tumours.

Keywords:

NBN, nijmegen breakage syndrome, NBN carriers, 657del5 founder mutation, R215W, I171V, BRCT domain, DNA repair.

Affiliation:

Department of Biology, University Roma Tre, Viale Guglielmo Marconi 446, I-00146 Roma, Italy.