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In multiple myeloma (MM), there are two distinct genetic subtypes based on copy number alterations and translocations. About half of all MM cases are a hyperdiploid type, which is characterized by multiple trisomies of chromosomes 3, 5, 7, 9 11, 15, 19 and 21 and a lower prevalence of primary translocations involving the immunoglobulin heavy chain (IgH) locus at 14q32. The remaining cases are the non-hyperdiploid type, and chromosomes 8, 13, 14, and 16 are frequently lost. Non-hyperdiploid myeloma is strongly association with translocations of IgH alleles with various partner chromosomes, such as t(11;14)(q13;q32), t(4;14)(p16.3; q32), t(14;16)(q32;q23), t(6;14)(p21;q32) or t(14;20) (q32;q11). The copy number alterations in other chromosome regions such as 1q, 6q, 8p, and 16q occur in both subtypes. Overall, non-hyperdiploid MM is associated with worse survival than hyperdiploid MM. In this study, we sequenced all exons of 409 cancer-related genes in matched tumor and normal DNA from 5 non-hyperdiploid MM patients using a next-generation semiconductor sequencing protocol. DNA was extracted from magnetic bead-enriched bone marrow CD138 positive tumor cells from the patients and CD138 negative cells were used as matched normal cells. We detected both point mutations and copy number variations (CNVs). One individual with refractory MM (IgG λ type, ISS stage II) displayed 8 non-synonymous somatic mutations in addition to numbers of CNVs including CCND1 and RB1. We observed 2 point mutations and 3 CNVs, affecting NF-kB pathway genes: IKBKB, CYLD, IKBKE, CD79B and SYK. Although the basis of NF-kB pathway activation is only partially understood, our findings greatly expand the mechanisms by which NF-kB may be activated in this patient. We also detected several gene alterations, which may be associated with poor prognosis and poor response to chemotherapy in patients with refractory MM. Although its value should be further confirmed in larger samples, the targeted next generation sequencing is a valuable tool for high-throughput genetic testing in clinical research. Citation Format: Hiroshi Ikeda, Yasushi Sasaki, Tetsuyuki Igarashi, Yuka Aoki, Toshiaki Hayashi, Tadao Ishida, Takashi Tokino, Yasuhisa Sinomura. Molecular diagnostics of drug resistant multiple myeloma cases using targeted next generation sequencing. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4424. doi:10.1158/1538-7445.AM2015-4424

Many risk factors have been proposed for systemic lupus erythematosus (SLE). However, there is little information about the relationship between lifestyles and SLE in Japan. Two case control studies were conducted in Kyushu, southern Japan, and in Hokkaido, northern Japan, to examine the relationship between lifestyles and development of SLE in females. The participants were 78 patients and 329 controls in Kyushu and 35 patients and 188 controls in Hokkaido. Smoking was associated with an increased risk of SLE after adjusting for age in both regions. However, in Hokkaido, this association between smoking and SLE did not reach statistical significance after adjusting for alcohol drinking. The present study suggests that smoking may increase the risk of SLE among Japanese females.