Non-C19MC-altered embryonal tumor with multilayered rosettes in a young woman with DICER1 syndrome: case report and review of the literature.

Embryonal tumors with multilayered rosettes (ETMR) are highly aggressive and therapy-resistant pediatric central nervous system (CNS) tumors that have three histological patters: embryonal tumor with abundant neuropil and true rosettes, ependymoblastoma, and medulloepithelioma. We present a case of ETMR in an 18-year-old woman with DICER1 syndrome. This report confirms the important role of DNA-methylation analysis in the classification of CNS embryonal tumors and the importance of investigating somatic and germline DICER1 mutations in all CNS embryonal tumors.

Cytogenetic characterization of NCI-H69 and NCI-H69AR small cell lung cancer cell lines by spectral karyotyping.

Small cell lung cancer (SCLC) shows an excellent sensitivity to chemotherapy, but commonly develops resistance after a few months. An early identification of a genomic marker in drug discovery may help to select patients who would respond to treatment in clinical trials. Herein, we characterized the parental NCI-H69 (sensitive) and NCI-H69AR (anthracycline-resistant) cell lines by G-banding and spectral karyotyping (SKY). In the H69 cell line, SKY allows us to redefine three alterations that are not well characterized by G-banding and to confirm seven. For H69AR, SKY redefined 10 chromosomal alterations and confirmed four observed by G-banding. Fluorescence in situ hybridization confirmed the amplification of the MYCN gene (dmin or hsr) in these two cell lines, although only the H69AR cell line showed MYCN amplification in the form of homogeneously staining regions. It should be noted that a new derivative chromosome appears in the H69AR cell line, a der(16)t(3;16;18;5;18), characterized by SKY as showing 18q amplification. Amplification of genes located in this region may correlate with resistance to anticancer therapies. We suggest that the 18q marker may have a broader application in SCLC. In conclusion, SKY provides a useful complementary technique to routine cytogenetics for the accurate characterization of SCLC cell lines and could provide some relevant information concerning regions involved in chemoresistance.

Genetic changes in small cell lung carcinoma.

Small cell lung carcinoma (SCLC) accounts for approximately 15% of all lung cancer cases. Despite a frequently good response to first-line treatment with chemotherapy and/or radiotherapy, early relapse occurs in the majority of patients and 5-year survival is only about 5%. Therefore, there is a need to develop novel treatments to improve the outcome of patients with SCLC. To fulfil this need, it is critical to gain further understanding on the molecular basis of SCLC and specifically to identify novel therapeutic targets. Clinical trials with molecularly targeted agents have been performed with little success in the past, but recently many promising oncogenic pathways have been discovered and novel targeted therapies are under evaluation. In this review, we summarise the most relevant genetic and signalling pathway alterations reported to date in SCLC and discuss the potential therapeutic implications of such events.