Minna, John Dorrance
Mayo Clinic
The University of Texas Southwestern Medical Center
Citations 12
EGFR-T790M Is a Rare Lung Cancer Susceptibility Allele with Enhanced Kinase Activity
Vikis, Haris G., Sato, Mitsuo , James, Michael A. , Wang, Daolong, Wang, Yian , Wang, Min , Jia, Dongmei , Liu, Yan , Bailey‐Wilson, Joan E. , Pinney, Susan M. , Petersen, Gloria M. , Wiest, Jonathan S., Fain, Pamela R., Schwartz, Ann G. , Gazdar, Adi F. , Gaba, Colette , Rothschild, Henry, Mandal, Diptasri , Kupert, Elena, Seminara, Daniela, Viswanathan, Avinash, Govindan, Ramaswamy , Anderson, Marshall W., You, Ming , Amos, Christopher I. , Andrade, Mariza de , Yang, Ping , Minna, John Dorrance , Wilson, Richard K , Pinney, Susan M , Govindan, Ramaswamy
Cancer Research | May 18, 2007 | Volume: 67 | Issue: 10 | Pages: 4665-4670
Abstract The use of tyrosine kinase inhibitors (TKI) has yielded great success in treatment of lung adenocarcinomas. However, patients who develop resistance to TKI treatment often acquire a somatic resistance mutation (T790M) located in the catalytic cleft of the epidermal growth factor receptor (EGFR) enzyme. Recently, a report describing EGFR-T790M as a germ-line mutation suggested that this mutation may be associated with inherited susceptibility to lung cancer. Contrary to previous reports, our analysis indicates that the T790M mutation confers increased Y992 and Y1068 phosphorylation levels. In a human bronchial epithelial cell line, overexpression of EGFR-T790M displayed a growth advantage over wild-type (WT) EGFR. We also screened 237 lung cancer family probands, in addition to 45 bronchoalveolar tumors, and found that none of them contained the EGFR-T790M mutation. Our observations show that EGFR-T790M provides a proliferative advantage with respect to WT EGFR and suggest that the enhanced kinase activity of this mutant is the basis for rare cases of inherited susceptibility to lung cancer. [Cancer Res 2007;67(10):4665–70]
Identification of a Novel Tumor Suppressor Gene p34 on Human Chromosome 6q25.1
Vikis, Haris G., Wang, Yian , Jia, Dongmei , Wang, Daolong, Bailey‐Wilson, Joan E. , Pinney, Susan M. , Petersen, Gloria M. , Wiest, Jonathan S., Fain, Pamela R., Schwartz, Ann G. , Gazdar, Adi F., Gaba, Colette , Rothschild, Henry, Mandal, Diptasri , Kupert, Elena, Seminara, Daniela, Liu, Yan , Viswanathan, Avinash, Govindan, Ramaswamy , Anderson, Marshall W., You, Ming , Wang, Min , Bierut, Laura Jean , Amos, Christopher I. , Andrade, Mariza de , Yang, Ping , Gazdar, Adi, Minna, John Dorrance , Wilson, Richard K , Pinney, Susan M , Govindan, Ramaswamy
Cancer Research | January 8, 2007 | Volume: 67 | Issue: 1 | Pages: 93-99
Abstract In this study, we observed loss of heterozygosity (LOH) in human chromosomal fragment 6q25.1 in sporadic lung cancer patients. LOH was observed in 65% of the 26 lung tumors examined and was narrowed down to a 2.2-Mb region. Single-nucleotide polymorphism (SNP) analysis of genes located within this region identified a candidate gene, termed p34. This gene, also designated as ZC3H12D, C6orf95, FLJ46041, or dJ281H8.1, carries an A/G nonsynonymous SNP at codon 106, which alters the amino acid from lysine to arginine. Nearly 73% of heterozygous lung cancer tissues with LOH and the A/G SNP also exhibited loss of the A allele. In vitro clonogenic and in vivo nude mouse studies showed that overexpression of the A allele exerts tumor suppressor function compared with the G allele. p34 is located within a recently mapped human lung cancer susceptibility locus, and association of the p34 A/G SNP was tested among these families. No significant association between the less frequent G allele and lung cancer susceptibility was found. Our results suggest that p34 may be a novel tumor suppressor gene involved in sporadic lung cancer but it seems not to be the candidate familial lung cancer susceptibility gene linked to chromosomal region 6q23-25. [Cancer Res 2007;67(1):93–9]