A research roadmap for next-generation sequencing informatics.

Next-generation sequencing technologies are fueling a wave of new diagnostic tests. Progress on a key set of nine research challenge areas will help generate the knowledge required to advance effectively these diagnostics to the clinic.

Familial aggregation of acute myeloid leukemia and myelodysplastic syndromes.

Purpose: Apart from rare pedigrees with multiple cases of acute myeloid leukemia (AML), there is limited data on familial aggregation of AML and myelodysplastic syndromes (MDSs) in the population.

Patients And Methods: Swedish population-based registry data were used to evaluate risk of AML, MDS, and other malignancies among 24,573 first-degree relatives of 6,962 patients with AML and 1,388 patients with MDS compared with 106,224 first-degree relatives of matched controls. We used a marginal survival model to calculate familial aggregation.

Genetic variants in DNA repair genes and the risk of cutaneous malignant melanoma in melanoma-prone families with/without CDKN2A mutations.

Cutaneous malignant melanoma (CMM) is an etiologically heterogeneous disease with genetic, environmental (sun exposure) and host (pigmentation/nevi) factors and their interactions contributing to risk. Genetic variants in DNA repair genes may be particularly important since their altered function in response to sun exposure-related DNA damage maybe related to risk for CMM. However, systematic evaluations of genetic variants in DNA repair genes are limited, particularly in high-risk families.

Association of human leukocyte antigens with nasopharyngeal carcinoma in high-risk multiplex families in Taiwan.

An association between specific human leukocyte antigens (HLA) alleles and nasopharyngeal carcinoma (NPC) has been reported for sporadic NPC, but studies of familial NPC are lacking. We evaluated this association with familial NPC in a study of 301 NPC cases and 1010 family and community controls from Taiwan. Class I HLA alleles were characterized using a sequence-based typing protocol.

Common genetic variants in candidate genes and risk of familial lymphoid malignancies.

Familial aggregation, linkage and case-control studies support the role of germline genes in the aetiology of lymphoid malignancies. To further examine the role of genetic variation underlying susceptibility, we analysed 1536 single nucleotide polymorphisms in 152 genes involved in apoptosis, DNA repair, immune response and oxidative stress pathways among a unique sample of 165 unrelated familial cases including patients with chronic lymphocytic leukaemia (CLL), Waldenström macroglobulinaemia (WM) and Hodgkin lymphoma (HL), and 107 spouse controls. We confirmed previous studies showing a polymorphism in the IL10 promoter (rs1800890/-3575T>A) to be associated with non-Hodgkin lymphoma, as this allele was found to be associated with both CLL and WM.