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PTEN Promoter Variants are not Associated with Common Cancers: Implications for Multigene Panel Testing.

Specialty Areas:
Date: November 7, 2017
Authors:
Brandon Smith, Holly Laduca, Jacob Clifford, Mary Helen Black, Rachid Karam, PhD, Robert Pilarski, Shuwei Li, Tina Pesaran, MA, MS, CGC
Journal: JCO Precision Oncology
Collaborators:
Read Abstract

Purpose PTEN mutations are associated with breast, colon, endometrial, kidney, and thyroid
cancers. Most PTEN promoter alterations, however, are characterized as variants of unknown
significance, and their contribution to cancer risk is unclear.
Materials and Methods Personal and family histories of 88,333 patients undergoing PTEN
analysis as part of multigene panel testing (MGPT) were retrospectively reviewed. Cases
(n = 59,784) wereindividuals with personal history ofPTEN-related cancer. Controls (n = 28,549)
had no personal history of cancer. Individuals were categorized as positive for one or more
mutations (PATHO), withoutmutations but carrying one or more promoter variant (PROM), or
negative for alterations (WT). Multivariable logistic regression was used to assess PTEN associations
with phenotypes, adjusted for race/ethnicity, age, sex, and MGPT.
Results Overall, 79 (0.09%) patients were PATHO and 791 (0.9%) were PROM carriers.
Compared with WT, PATHOs were 2.30 (95% CI, 1.19 to 4.72) times as likely to have breast,
7.23 (95% CI, 2.74 to 19.14) times as likely to have bilateral/multiple primary breast, and 7.56
(95% CI, 1.97 to 23.98) times as likely to have uterine/endometrial cancer. PROMs were not
significantly more likely than WT to have cancer (all 0.84 < odds ratio .05).
Conclusion PTEN promoter variants were not associated with cancer. These results do not
support the inclusion of PTEN promoter sequencing in MGPT.