A missense somatic mutation in JAK2 gene (JAK2 V617F) has recently been reported in chronic myeloproliferative disorders, including polycythemia vera, essential thrombocythemia and myelofibrosis with myeloid metaplasia, strongly suggesting its role in the pathogenesis of myeloid disorders. As activation of JAK2 signaling is occurred in other malignancies as well, we have analysed 558 tissues from common human cancers, including colon, breast and lung carcinomas, and 143 acute adulthood leukemias by polymerase chain reaction -single strand conformation polymorphism analysis. We found three JAK2 mutations in the 113 acute myelogenous leukemias (AMLs) (2.7%), but none in other cancers. The mutations consisted of two V617F mutations and one K607N mutation. None of the AML patients with the JAK2 V617F mutation had a history of previous hematologic disorders. This is the first report on the JAK2 gene mutation in AML, and the data indicated that the JAK2 gene mutation may not only contribute to the development of chronic myeloid disorders, but also to some AMLs.

Fas, a cell surface receptor and member of the tumour necrosis factor receptor superfamily, induces apoptosis upon oligomerization by its ligand (Fas ligand: FasL). Detailed studies have revealed that Fas is broadly expressed in normal human tissues, but relatively little is known about the range of cell types capable of expressing FasL. The aim of this study was to determine the in vivo patterns of expression of Fas and FasL in human skin tissues. Immunohistochemistry was performed using paraffin-embedded samples of normal and neoplastic skin tissues. In normal skin, FasL was expressed in the epidermis, sebaceous glands, sweat glands and outer root sheath of the hair. In squamous cell carcinomas (SCC), all cases analysed expressed FasL at high levels, whereas 60% of basal cell carcinomas (BCC) were positive for FasL. Expression of Fas in normal skin was observed in the basal and spinous layers of the epidermis, the outer root sheath of the hair, and the sebaceous glands. Expression of Fas was observed in all the SCC tested and none of the BCC tested. Expression of FasL by normal cells and tumour cells in skin tissue, demonstrated for the first time in the present study, may provide an important clue to understanding skin physiology, and immune evasion of skin tumours.

Ras proteins control signalling pathways that are key regulators of several aspects of normal cell growth and malignant transformation. BRAF, which encodes an RAF family member in the downstream pathway of RAS, is somatically mutated in a number of human cancers. The activating mutation of BRAF is known to play a role in tumour development. As there have been no data on the BRAF mutation in non-Hodgkin's lymphoma (NHL), we analysed the genomic DNAs from 164 NHLs by polymerase chain reaction (PCR)-based single-strand conformation polymorphism (SSCP) for the detection of somatic mutations of BRAF (exons 11 and 15). Overall, we detected BRAF mutations in four NHLs (2.4%). Whereas most BRAF mutations in human cancers involved V599 of BRAF, all of the four BRAF mutations in the NHLs involved other amino acids (one G468A, two G468R and one D593G). To our knowledge, this is the first report on BRAF mutation in NHL, and the data indicate that BRAF is occasionally mutated in NHL, and suggest that BRAF mutation may contribute to the tumour development in some NHLs.

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The ATBF1 gene may contribute to the development of HCCs via transcriptional down-regulation of mRNA expression, but not by genetic or epigenetic alterations.