TY - JOUR
T1 - Hotspot mutation panel testing reveals clonal evolution in a study of 265 paired primary and metastatic tumors
AU - Goswami, Rashmi S.
AU - Patel, Keyur P.
AU - Singh, Rajesh R.
AU - Meric-Bernstam, Funda
AU - Kopetz, E. Scott
AU - Subbiah, Vivek
AU - Alvarez, Ricardo H.
AU - Davies, Michael A.
AU - Jabbar, Kausar J.
AU - Roy-Chowdhuri, Sinchita
AU - Lazar, Alexander J.
AU - Medeiros, L. Jeffrey
AU - Broaddus, Russell R.
AU - Luthra, Rajyalakshmi
AU - Routbort, Mark J.
N1 - Publisher Copyright:
© 2014 American Association for Cancer Research.
PY - 2015/6/1
Y1 - 2015/6/1
N2 - Purpose: We used a clinical next-generation sequencing (NGS) hotspot mutation panel to investigate clonal evolution in paired primary and metastatic tumors. Experimental Design: A total of 265 primary and metastatic tumor pairs were sequenced using a 46-gene cancer mutation panel capable of detecting one or more single-nucleotide variants as well as small insertions/deletions. Mutations were tabulated together with tumor type and percentage, mutational variant frequency, time interval between onset of primary tumor and metastasis, and neoadjuvant therapy status. Results: Of note, 227 of 265 (85.7%) tumor metastasis pairs showed identical mutation calls. Of the tumor pairs with identical mutation calls, 160 (60.4%) possessed defining somatic mutation signatures and 67 (25.3%) did not exhibit any somatic mutations. There were 38 (14.3%) cases that showed at least one novel mutation call between the primary and metastasis. Metastases were almost two times more likely to show novel mutations (n = 20, 7.5%) than primary tumors (n = 12, 4.5%). TP53 was the most common additionally mutated gene in metastatic lesions, followed by PIK3CA and SMAD4. PIK3CA mutations were more often associated with metastasis in colon carcinoma samples. Conclusions: Clinical NGS hotspot panels can be useful in analyzing clonal evolution within tumors as well as in determining subclonal mutations that can expand in future metastases. PIK3CA, SMAD4, and TP53 are most often involved in clonal divergence, providing potential targets that may help guide the clinical management of tumor progression or metastases.
AB - Purpose: We used a clinical next-generation sequencing (NGS) hotspot mutation panel to investigate clonal evolution in paired primary and metastatic tumors. Experimental Design: A total of 265 primary and metastatic tumor pairs were sequenced using a 46-gene cancer mutation panel capable of detecting one or more single-nucleotide variants as well as small insertions/deletions. Mutations were tabulated together with tumor type and percentage, mutational variant frequency, time interval between onset of primary tumor and metastasis, and neoadjuvant therapy status. Results: Of note, 227 of 265 (85.7%) tumor metastasis pairs showed identical mutation calls. Of the tumor pairs with identical mutation calls, 160 (60.4%) possessed defining somatic mutation signatures and 67 (25.3%) did not exhibit any somatic mutations. There were 38 (14.3%) cases that showed at least one novel mutation call between the primary and metastasis. Metastases were almost two times more likely to show novel mutations (n = 20, 7.5%) than primary tumors (n = 12, 4.5%). TP53 was the most common additionally mutated gene in metastatic lesions, followed by PIK3CA and SMAD4. PIK3CA mutations were more often associated with metastasis in colon carcinoma samples. Conclusions: Clinical NGS hotspot panels can be useful in analyzing clonal evolution within tumors as well as in determining subclonal mutations that can expand in future metastases. PIK3CA, SMAD4, and TP53 are most often involved in clonal divergence, providing potential targets that may help guide the clinical management of tumor progression or metastases.
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U2 - 10.1158/1078-0432.CCR-14-2391
DO - 10.1158/1078-0432.CCR-14-2391
M3 - Article
C2 - 25695693
AN - SCOPUS:84942279918
SN - 1078-0432
VL - 21
SP - 2644
EP - 2651
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 11
ER -