ABSTRACT
Recent advances in genomic technologies have revolutionized acute myeloid leukemia (AML) understanding by identifying potential novel actionable genomic alterations. Consequently, current risk stratification at diagnosis not only relies on cytogenetics, but also on the inclusion of several of these abnormalities. Despite this progress, AML remains a heterogeneous and complex malignancy with variable response to current therapy. Although copy-number alterations (CNAs) are accepted prognostic markers in cancers, large-scale genomic studies aiming at identifying specific prognostic CNA-based markers in AML are still lacking. Using 367 AML, we identified four recurrent CNA on chromosomes 11 and 21 that predicted outcome even after adjusting for standard prognostic risk factors and potentially delineated two new subclasses of AML with poor prognosis. ERG amplification, the most frequent CNA, was related to cytarabine resistance, a cornerstone drug of AML therapy. These findings were further validated in The Cancer Genome Atlas data. Our results demonstrate that specific CNA are of independent prognostic relevance, and provide new molecular information into the genomic basis of AML and cytarabine response. Finally, these CNA identified two potential novel risk groups of AML, which when confirmed prospectively, may improve the clinical risk stratification and potentially the AML outcome.
Subject(s)
Biomarkers, Tumor , DNA Copy Number Variations , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/mortality , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cohort Studies , Drug Resistance, Neoplasm , Female , Gene Dosage , Genes, p53 , Genetic Association Studies , Genetic Predisposition to Disease , Genome-Wide Association Study , Genomics/methods , Humans , Leukemia, Myeloid, Acute/diagnosis , Leukemia, Myeloid, Acute/therapy , Male , Middle Aged , Mutation , Polymorphism, Single Nucleotide , Prognosis , Proportional Hazards Models , Treatment OutcomeABSTRACT
A progressive papular eruption on the face, limbs and vulva had been present for seven years in a 38-year old female patient. Some papules were small and confluent while others were sparse, as in nodular prurigo. Histology showed massive proliferation of the follicular sheath epithelium, connected to the lower surface of the epidermis. The lesion formed a plate-like area very similar to that observed in superficial basal cell carcinoma and corresponding to a tumour of the follicular infundibulum. Remarkable features of this case were the large number of lesions, their photosensitivity (they became pruriginous and increased in size after exposure to the sun), the presence of eccrine sweat glands beneath a skin lesion of the thigh, the basal cell degeneration of two lesions and the slight improvement observed after etretinate therapy. To our knowledge, such findings have not yet been reported in tumours of the follicular infundibulum.
Subject(s)
Carcinoma, Basal Cell/pathology , Hair Diseases/pathology , Skin Neoplasms/pathology , Adult , Carcinoma, Basal Cell/drug therapy , Diagnosis, Differential , Etretinate/therapeutic use , Female , Hair Diseases/drug therapy , Humans , Photosensitivity Disorders/etiology , Skin Neoplasms/drug therapyABSTRACT
Carcinoid tumor primarily developing in the thymus gland is very rare. A new case is reported to add to the 35 previously reported. In most cases, patients have no endocrinological syndrome; the tumor is rarely associated with a multiple endocrine adenomatosis. This neoplasm probably derived from Kultschizky cells which are present in the normal thymus gland. Histologically they are very similar to the carcinoid tumor of other organs. Complete surgical excision is the best treatment when possible.
