1.
A novel COL4A5 mutation identified in a Chinese Han family using exome sequencing.
Xiu, X, Yuan, J, Deng, X, Xiao, J, Xu, H, Zeng, Z, Guan, L, Xu, F, Deng, S
BioMed research international. 2014;:186048
Abstract
Alport syndrome (AS) is a monogenic disease of the basement membrane (BM), resulting in progressive renal failure due to glomerulonephropathy, variable sensorineural hearing loss, and ocular anomalies. It is caused by mutations in the collagen type IV alpha-3 gene (COL4A3), the collagen type IV alpha-4 gene (COL4A4), and the collagen type IV alpha-5 gene (COL4A5), which encodes type IV collagen α3, α4, and α5 chains, respectively. To explore the disease-related gene in a four-generation Chinese Han pedigree of AS, exome sequencing was conducted on the proband, and a novel deletion mutation c.499delC (p.Pro167Glnfs*36) in the COL4A5 gene was identified. This mutation, absent in 1,000 genomes project, HapMap, dbSNP132, YH1 databases, and 100 normal controls, cosegregated with patients in the family. Neither sensorineural hearing loss nor typical COL4A5-related ocular abnormalities (dot-and-fleck retinopathy, anterior lenticonus, and the rare posterior polymorphous corneal dystrophy) were present in patients of this family. The phenotypes of patients in this AS family were characterized by early onset-age and rapidly developing into end-stage renal disease (ESRD). Our discovery broadens the mutation spectrum in the COL4A5 gene associated with AS, which may also shed new light on genetic counseling for AS.
2.
The efficacy and safety of panitumumab administered concomitantly with FOLFIRI or Irinotecan in second-line therapy for metastatic colorectal cancer: the secondary analysis from STEPP (Skin Toxicity Evaluation Protocol With Panitumumab) by KRAS status.
Mitchell, EP, Piperdi, B, Lacouture, ME, Shearer, H, Iannotti, N, Pillai, MV, Xu, F, Yassine, M
Clinical colorectal cancer. 2011;(4):333-9
Abstract
BACKGROUND Panitumumab, a fully human monoclonal antibody targeting the epidermal growth factor receptor (EGFR), is used as monotherapy for chemorefractory metastatic colorectal cancer (mCRC) in patients with wild-type (WT) KRAS tumors. Although skin toxicities are the most common adverse events associated with EGFR inhibitors, the differences in efficacy and safety between pre-emptive and reactive skin treatment according to KRAS tumor status has not been reported. PATIENTS AND METHODS Eligible patients had mCRC with disease progression or unacceptable toxicity with first-line treatment containing fluoropyrimidine and oxaliplatin-based chemotherapy ± bevacizumab. Patients were randomized 1:1 to pre-emptive or reactive skin treatment (after skin toxicity developed). Patients received either panitumumab 6 mg/kg + FOLFIRI every 2 weeks or panitumumab 9 mg/kg + irinotecan every 3 weeks. Key study endpoints included overall response rate (ORR), overall survival, progression-free survival (PFS), and safety according to KRAS tumor status. RESULTS Eighty-seven (92%) of 95 enrolled patients had evaluable KRAS tumor status: 49 (56%) patients with WT and 38 (44%) patients with mutant (MT) KRAS tumors, respectively. The ORR was 16% and 8% for patients with WT and MT KRAS tumors, respectively. Median PFS was 5.5 and 3.3 months for patients with WT and MT KRAS tumors, respectively. The most commonly observed adverse events by KRAS tumor status included dermatitis acneiform and pruritus. CONCLUSION Panitumumab in combination with irinotecan-based chemotherapy has an acceptable toxicity profile in second-line therapy for mCRC. Numerical differences trending in favor of the patients with WT KRAS tumors were observed for most efficacy endpoints.