Low-Frequency Mutational Heterogeneity of Invasive Ductal Carcinoma Subtypes: Information to Direct Precision Oncology
Low-Frequency Mutational Heterogeneity of Invasive Ductal Carcinoma Subtypes: Information to Direct Precision Oncology
复制标题
浸润性导管癌亚型的低频突变异质性：指导精准肿瘤学的信息
DOI：
10.3390/ijms20051011
复制
发表时间：
2019
影响因子：
5.6
通讯作者：
B. Parsons
中科院分区：
文献类型：
--
作者：
Meagan B. Myers;Karen L. McKim;M. Banda;N. George;B. Parsons
Information regarding the role of low-frequency hotspot cancer-driver mutations (CDMs) in breast carcinogenesis and therapeutic response is limited. Using the sensitive and quantitative Allele-specific Competitor Blocker PCR (ACB-PCR) approach, mutant fractions (MFs) of six CDMs (PIK3CA H1047R and E545K, KRAS G12D and G12V, HRAS G12D, and BRAF V600E) were quantified in invasive ductal carcinomas (IDCs; including ~20 samples per subtype). Measurable levels (i.e., ≥ 1 × 10−5, the lowest ACB-PCR standard employed) of the PIK3CA H1047R, PIK3CA E545K, KRAS G12D, KRAS G12V, HRAS G12D, and BRAF V600E mutations were observed in 34/81 (42%), 29/81 (36%), 51/81 (63%), 9/81 (11%), 70/81 (86%), and 48/81 (59%) of IDCs, respectively. Correlation analysis using available clinicopathological information revealed that PIK3CA H1047R and BRAF V600E MFs correlate positively with maximum tumor dimension. Analysis of IDC subtypes revealed minor mutant subpopulations of critical genes in the MAP kinase pathway (KRAS, HRAS, and BRAF) were prevalent across IDC subtypes. Few triple-negative breast cancers (TNBCs) had appreciable levels of PIK3CA mutation, suggesting that individuals with TNBC may be less responsive to inhibitors of the PI3K/AKT/mTOR pathway. These results suggest that low-frequency hotspot CDMs contribute significantly to the intertumoral and intratumoral genetic heterogeneity of IDCs, which has the potential to impact precision oncology approaches.
登录
查看更多内容
影响因子：
11.2
作者：
Janku F;Wheler JJ;Naing A;Falchook GS;Hong DS;Stepanek VM;Fu S;Piha-Paul SA;Lee JJ;Luthra R;Tsimberidou AM;Kurzrock R
通讯作者：
Kurzrock R
影响因子：
4.6
作者：
M. E. Hammond;Daniel F. Hayes;M. Dowsett;D. C. Allred;K. Hagerty;S. Badve;P. Fitzgibbons;G. Francis
通讯作者：
M. E. Hammond;Daniel F. Hayes;M. Dowsett;D. C. Allred;K. Hagerty;S. Badve;P. Fitzgibbons;G. Francis
获得的BRAF抑制剂耐药性：耐药机制的光谱和频率，临床行为和表型关联的多中心荟萃分析。
DOI：
10.1016/j.ejca.2015.08.022
发表时间：
2015-12
期刊：
European journal of cancer (Oxford, England : 1990)
影响因子：
--
作者：
Johnson DB;Menzies AM;Zimmer L;Eroglu Z;Ye F;Zhao S;Rizos H;Sucker A;Scolyer RA;Gutzmer R;Gogas H;Kefford RF;Thompson JF;Becker JC;Berking C;Egberts F;Loquai C;Goldinger SM;Pupo GM;Hugo W;Kong X;Garraway LA;Sosman JA;Ribas A;Lo RS;Long GV;Schadendorf D
通讯作者：
Schadendorf D
影响因子：
2.3
作者：
Myers MB;McKim KL;Meng F;Parsons BL
通讯作者：
Parsons BL
影响因子：
120.7
作者：
Carey, Lisa A.;Perou, Charles M.;Millikan, Robert C.
通讯作者：
Millikan, Robert C.