Comparison of solid tumor mutations under the targeted agent and profiling utilization registry (TAPUR) study: how do gynecologic cancers compare with others?

Abstract

<h3>Objectives:</h3> Targetable somatic mutations in solid tumors have led to the incorporation of numerous biologic agents for gynecologic and other cancers, including <i>BRCA</i> with PARP inhibitors, <i>ATM</i> and <i>POLE</i> with immunotherapies, and <i>PIK3CA</i> with mTOR inhibitors. However, it is unclear how frequently these mutations are expressed in gynecologic and other cancers. We sought to evaluate the genomic expression of various cancers using a landmark cancer genomics program from the National Cancer Institute. <h3>Methods:</h3> Data from the Cancer Genome Atlas (TCGA) were extrapolated, including mutations in genes associated with ovarian, uterine, cervical, breast, colon, lung cancer and melanoma: <i>BRCA1/2, POLE, ERBB2, PIK3CA, CDKN2A, ATM, BRAF, FGFR1,2,3.</i> Chi-square analysis was used to compare genetic expression across different tumor types. <h3>Results:</h3> A total of 3,677 tumor specimens; of which 436 ovarian, 530 uterine, 289 cervical, 986 breast, 400 colon, 567 lung, and 469 melanoma were included in our analysis. Based on somatic mutations, <i>BRCA1/2</i> were found on average in 13.58% of these solid tumors, <i>POLE</i> in 7.49%, <i>PIK3CA</i> in 22.53% and <i>ERBB2</i> in 5.30%. <i>BRCA1/2</i> mutations for which PARP inhibitors are used were expressed in 10% of ovarian, 28.49% uterine, 10.03% cervix, 5.88% breast, 14.25% colon, 11.46% lung, and 14.92% melanoma. <i>POLE</i> mutations for which immunotherapies are indicated were identified in 2.98% ovarian, 17.17% uterine, 4.5% cervical, 1.62% breast, 9% colon, 6.7% lung, and 10.45% melanoma. <i>PIK3CA</i> mutations for which mTOR inhibitors are effective were found in 3.67% ovarian, 51.13% uterine, 29.41% cervical, 34.38% breast, 31% colon, 4.94% lung, and 3.2% melanoma. <i>ERBB2</i> mutations were observed in 1.83% ovarian, 3.45% breast, 5.88% cervical, 10.19% uterine, 6.50% colon, and 5.54% melanoma cases. Other actionable mutations including <i>CDKN2A, ATM, BRAF,</i> and <i>ERBB3</i> that can be targeted by other biologic therapies were also evaluated in these various tumor types. <h3>Conclusions:</h3> The expression of <i>BRCA1/2, POLE, PIK3CA</i> and other genomic markers appear to be prevalent in gynecologic and other cancers. These biomarkers with associated biologic therapies have guided our current trial enrollment and may have direct clinical implications toward personalized treatment for patients with solid tumors. Further research is warranted to understand the unique tumor microenvironments that cause varying efficacy of targetable therapies across different tumor subtypes.