Inherited mutations in the BRCA1 gene confer increased susceptibility to breast and ovarian cancer. Its role in sporadic carcinogenesis is not well de®ned. Somatic mutations in breast cancers have not been reported and to date there are only three reports of somatic mutations in sporadic ovarian cancers. To investigate the contribution of BRCA1 mutations to sporadic breast and ovarian cancer in the Chinese population, we analysed 62 samples from Chinese women using the protein truncation test. There were 40 cases of breast cancer under age 50 and 22 cases of ovarian cancer, all unselected for family history. There was no age selection for the ovarian cancers. We found two somatic BRCA1 mutations in exon 11, one in a breast cancer and the other in an ovarian cancer, both of which result in truncated proteins. Our results indicate that somatic BRCA1 mutations, like somatic mutations in the BRCA2 gene, though very rare, can be found in both breast and ovarian cancers and support a tumor suppressor function for BRCA1 in sporadic tumors.Keywords: BRCA1; somatic mutations; breast cancer; ovarian cancer; ChineseThe observed high incidence of loss of heterozygosity in the BRCA1 region in breast and ovarian tumors suggested the presence of somatic mutations in this gene. After the BRCA1 gene was cloned, Futreal et al. (1994) actively attempted to demonstrate this but failed to ®nd any somatic mutations in the 36 breast and 12 ovarian carcinomas they studied which showed LOH at the BRCA1 locus. The ®rst evidence for somatic BRCA1 mutations came from Merajver et al. (1995), who described such mutations in four of their 47 ovarian cases studied. A further somatic mutation in an ovarian cancer was described by Hosking et al. (1995) and a few more have been reported recently by Berchuck et al. (1998). No somatic BRCA1 mutation has ever been reported from breast cancer.Molecular studies of BRCA1 mutations have generally been focused on Caucasian high-risk families (Szabo and King, 1997). The Japanese are the only Asian population in the literature so far. Both Katagiri et al. (1996) and Matsushima et al. (1996) have reported a lower incidence of 3.8 and 5% in their breast and ovarian cancer population respectively. To investigate the contribution of BRCA1 mutations in the Chinese population of Hong Kong, we analysed a series of 40 breast and 22 ovarian cancer tumor samples from Chinese women, all cases being unselected for family history.Sixty-two rapidly frozen fresh tumor specimens were obtained from mastectomy or excision specimens of patients treated for breast carcinoma in Queen Mary Hospital, Tung Wah and Pamela Youde Nethersole Hospitals, Hong Kong; and from excision specimens of patients with ovarian carcinoma in Queen Mary Hospital. Breast cancer cases diagnosed under the age of 50 were selected for this study. Fifteen of the breast cancer patients were between ages 41 ± 50, whereas the remaining 13 and 12 were between the ages 21 ± 35 and 36 ± 40, respectively. There was no age selection for the ovarian cancers which...

STAT6 (signal transducer and activator of transcription 6) is a transcription factor that plays a central role in the pathophysiology of allergic inflammation. We have identified 16 patients from 10 families spanning three continents with a profound phenotype of early-life onset allergic immune dysregulation, widespread treatment-resistant atopic dermatitis, hypereosinophilia with esosinophilic gastrointestinal disease, asthma, elevated serum IgE, IgE-mediated food allergies, and anaphylaxis. The cases were either sporadic (seven kindreds) or followed an autosomal dominant inheritance pattern (three kindreds). All patients carried monoallelic rare variants in STAT6 and functional studies established their gain-of-function (GOF) phenotype with sustained STAT6 phosphorylation, increased STAT6 target gene expression, and TH2 skewing. Precision treatment with the anti–IL-4Rα antibody, dupilumab, was highly effective improving both clinical manifestations and immunological biomarkers. This study identifies heterozygous GOF variants in STAT6 as a novel autosomal dominant allergic disorder. We anticipate that our discovery of multiple kindreds with germline STAT6 GOF variants will facilitate the recognition of more affected individuals and the full definition of this new primary atopic disorder.

Among the various renal lesions after HSCT, membranous glomerulonephritis and thrombotic microangiopathy were the most common. Mechanisms of renal injury varied from graft-versus-host disease-associated immune complex deposition to non-immune complex injury on endothelial cells, glomerular epithelial cells and tubular epithelium. Pathologists and clinicians should attend to the histological and temporal heterogeneity of renal injury when managing patients after HSCT.

Antiglomerular basement membrane disease is uncommon among the Chinese population. It predominantly affects older patients, and prognosis is poor. Long-term preservation of renal function after the initial attack is unusual.