Hereditary predisposition syndromes to malignant hemopathies (HPSMH)

Salomé Dupriez1, Augustin Ferrant1, Marie-Christiane Vekemans1, Bénédicte Brichard1, Lucienne Michaux1, Thierry Connerotte2, Eric Van Den Neste1, Christiane Vermylen1, Laurent Knoops1, Carlos Graux3, François Duhoux1, Catherine Lambert1, Xavier Poiré1, Hélène Antoine-Poirel1,4
1 Cliniques universitaires Saint-Luc – UCL, Brussels
2 Cliniques saint-Pierre, Ottignies
3 CHU Dinnant Mont-Godinne – UCL, Yvoir
4 Belgian Cancer Registry

HPSMH are underdiagnosed (1%) compared to solid tumors (5-10%). Owing to the emergence of new sequencing technologies, nearly a hundred of new predisposing genes, have been identified. Nowadays, we estimate that 10% of malignant myeloid hemopathies may have a genetic predisposition. HPSMH are important to identify for several reasons: to set up a suitable follow-up program as well as an attenuated allograft conditioning in case of Fanconia anemia or telomeropathies; to select adequate donor without the familial predisposing mutation in case of familial allograft; to perform pre-symptomatic diagnosis in relatives and to implement a prevention program.

The objective of this retrospective monocentric study is to contribute to a better identification of patients having HPSMH and to propose guidelines for identification and for the follow-up in case of predisposing mutation. A retrospective census was carried out by selecting Belgian Francophone families or individuals having suffered from several cancers (named as “families”), including at least one malignant hemopathy. 

252 persons belonging to 117 “families” were included. Predisposing gene mutations in 8 “families” (6,8%) were detected. The retrospective analysis allowed us to suspect a candidate gene in 22 additional “families” (18,8%). Unfortunately, there were no available material or the patients were lost of follow-up.

Our recommendations based on the literature and our observations are:
1. Investigation in 3 circumstances: familial and/or personal history suggestive of a HPSHM; potential HPSHM-type germline mutation found in malignant cells; evaluation of hematopoietic stem cell donors.
2. Oncogenetic counseling for patients having suggestive HPSHM features to propose genetic tests on candidate genes on uninvaded cells such as fibroblast cell culture, hairs or nails.
3. Specific clinical management of patients as well as pre-symptomatic genetic testing for relatives, if an inherited mutation is identified, with a close collaboration between hematology and genetics.