Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2011 Aug 9;105(4):586-91.
doi: 10.1038/bjc.2011.266. Epub 2011 Jul 26.

Lymphoid tumours and breast cancer in ataxia telangiectasia; substantial protective effect of residual ATM kinase activity against childhood tumours

A Reiman  1 , V Srinivasan, G Barone, J I Last, L L Wootton, E G Davies, M M Verhagen, M A Willemsen, C M Weemaes, P J Byrd, L Izatt, D F Easton, D J Thompson, A M Taylor
Affiliations

Lymphoid tumours and breast cancer in ataxia telangiectasia; substantial protective effect of residual ATM kinase activity against childhood tumours

A Reiman et al. Br J Cancer. .

Abstract

Background: Immunodeficiency in ataxia telangiectasia (A-T) is less severe in patients expressing some mutant or normal ATM kinase activity. We, therefore, determined whether expression of residual ATM kinase activity also protected against tumour development in A-T.

Methods: From a total of 296 consecutive genetically confirmed A-T patients from the British Isles and the Netherlands, we identified 66 patients who developed a malignant tumour; 47 lymphoid tumours and 19 non-lymphoid tumours were diagnosed. We determined their ATM mutations, and whether cells from these patients expressed any ATM with residual ATM kinase activity.

Results: In childhood, total absence of ATM kinase activity was associated, almost exclusively, with development of lymphoid tumours. There was an overwhelming preponderance of tumours in patients <16 years without kinase activity compared with those with some residual activity, consistent with a substantial protective effect of residual ATM kinase activity against tumour development in childhood. In addition, the presence of eight breast cancers in A-T patients, a 30-fold increased risk, establishes breast cancer as part of the A-T phenotype.

Conclusion: Overall, a spectrum of tumour types is associated with A-T, consistent with involvement of ATM in different mechanisms of tumour formation. Tumour type was influenced by ATM allelic heterogeneity, residual ATM kinase activity and age.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Kaplan–Meier survival to cancer diagnosis by ATM kinase activity. Shaded areas are 95% CIs. The solid line is for A-T patients with no ATM kinase activity, and the dashed line is for patients with some kinase activity. The values under the graph refer to the number of patients in each group at risk at the corresponding analysis time.
See this image and copyright information in PMC

References

    1. Angele S, Lauge A, Fernet M, Moullan N, Beauvais P, Couturier J, Stoppa-Lyonnet D, Hall J (2003) Phenotypic cellular characterization of an ataxia telangiectasia patient carrying a causal homozygous missense mutation. Hum Mutat 21(2): 169–170 - PubMed
    1. Antoniou AC, Cunningham AP, Peto J, Evans DG, Lalloo F, Narod SA, Risch HA, Eyfjord JE, Hopper JL, Southey MC, Olsson H, Johannsson O, Borg A, Pasini B, Radice P, Manoukian S, Eccles DM, Tang N, Olah E, Anton-Culver H, Warner E, Lubinski J, Gronwald J, Gorski B, Tryggvadottir L, Syrjakoski K, Kallioniemi OP, Eerola H, Nevanlinna H, Pharoah PD, Easton DF (2008) The BOADICEA model of genetic susceptibility to breast and ovarian cancers: updates and extensions. Br J Cancer 98(8): 1457–1466 - PMC - PubMed
    1. Austen B, Barone G, Reiman A, Byrd PJ, Baker C, Starczynski J, Nobbs MC, Murphy RP, Enright H, Chaila E, Quinn J, Stankovic T, Pratt G, Taylor AM (2008) Pathogenic ATM mutations occur rarely in a subset of multiple myeloma patients. Br J Haematol 142(6): 925–933 - PubMed
    1. Barone G, Groom A, Reiman A, Srinivasan V, Byrd PJ, Taylor AM (2009) Modeling ATM mutant proteins from missense changes confirms retained kinase activity. Hum Mutat 30(8): 1222–1230 - PubMed
    1. Bredemeyer AL, Huang CY, Walker LM, Bassing CH, Sleckman BP (2008) Aberrant V(D)J recombination in ataxia telangiectasia mutated-deficient lymphocytes is dependent on nonhomologous DNA end joining. J Immunol 181(4): 2620–2625 - PMC - PubMed

Publication types

MeSH terms

Substances