Prognostic significance of biallelic loss of PTEN in clear cell renal cell carcinoma.
OBJECTIVE
We investigated the clinical implications of biallelic loss of PTEN in clear cell renal cell carcinoma and whether PTEN biallelic loss would induce p53 dependent cellular senescence.


METHODS
Data were obtained using the CGDS-R package from the TCGA data set kirc_tcga_pub. PTEN allelic status was classified into 3 groups, including biallelic PTEN loss (homozygous deletion or combined heterozygous deletion and mutation), monoallelic PTEN loss (heterozygous deletion or mutation) and absent allelic loss. Univariate and multivariate overall survival analysis was performed. TP53 allelic loss and mean expression of genes related to p53 dependent cellular senescence were compared.


RESULTS
Of 416 patients with clear cell renal cell carcinoma 11 (2.6%) had biallelic PTEN loss and 69 (16.6%) had monoallelic loss. PTEN allelic loss was associated with late tumor stage and high histological grade. Patients with biallelic loss showed worse overall survival after adjusting for age and AJCC tumor stage (HR 3.1, 95% CI 1.4-6.8, p = 0.005). About half of the patients with PTEN biallelic loss had accompanying TP53 allelic loss. Biallelic loss of PTEN did not increase the expression of genes related to p53 dependent cellular senescence.


CONCLUSIONS
PTEN biallelic loss may be a prognostic marker for clear cell renal cell carcinoma. It does not seem to induce p53 dependent cellular senescence, partly due to allelic loss of TP53.
Program for Certified Physicians in BioMedical Informatics, Korean Society of Medical Informatics, Seoul, Republic of Korea; Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Hee Jin
HJ
Lee
Program for Certified Physicians in BioMedical Informatics, Korean Society of Medical Informatics, Seoul, Republic of Korea; Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Ho Yun
HY
Lee
Program for Certified Physicians in BioMedical Informatics, Korean Society of Medical Informatics, Seoul, Republic of Korea; Department of Pathology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, Republic of Korea.
Jeong Hee
JH
Lee
Program for Certified Physicians in BioMedical Informatics, Korean Society of Medical Informatics, Seoul, Republic of Korea; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
Hajeong
H
Lee
Program for Certified Physicians in BioMedical Informatics, Korean Society of Medical Informatics, Seoul, Republic of Korea; Department of Pathology, Inje University Sanggye Paik Hospital, Inje University College of Medicine, Seoul, Republic of Korea.
Guhyun
G
Kang
Program for Certified Physicians in BioMedical Informatics, Korean Society of Medical Informatics, Seoul, Republic of Korea; Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Joon Seon
JS
Song
Program for Certified Physicians in BioMedical Informatics, Korean Society of Medical Informatics, Seoul, Republic of Korea; Department of Pathology, Inchun St. Mary's Hospital, Catholic University of Korea, Inchun, Republic of Korea. Electronic address: jkang.alien@gmail.com.
Jun
J
Kang
Systems Biomedical Informatics National Core Research Center, Seoul National University College of Medicine, Seoul, Republic of Korea; Division of Biomedical Informatics, Seoul National University Biomedical Informatics, Seoul, Republic of Korea.
Ju Han
JH
Kim
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000235:genetics*; D016922:Cellular Senescence / Q000235:genetics; D005260:Female; D016158:Genes, p53 / Q000502:physiology; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics*; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D011379:Prognosis
D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
PTEN protein; carcinoma; haploinsufficiency; high-throughput nucleotide sequencing; human; kidney; renal cell