PMID- 30361826 OWN - NLM STAT- MEDLINE DCOM- 20190527 LR - 20220802 IS - 2211-3436 (Electronic) IS - 2211-3428 (Linking) VI - 42 IP - 1 DP - 2019 Feb TI - Molecular features unique to glioblastoma radiation resistant residual cells may affect patient outcome - a short report. PG - 107-116 LID - 10.1007/s13402-018-0411-7 [doi] AB - PURPOSE: Previously we have shown, using a primary glioblastoma (GBM) cell model, that a subpopulation of innately radiation resistant (RR) GBM cells survive radiotherapy and form multinucleated and giant cells (MNGCs) by homotypic fusions. We also showed that MNGCs may cause relapse. Here, we set out to explore whether molecular characteristics of RR cells captured from patient-derived primary GBM cultures bear clinical relevance. METHODS: Primary cultures were derived from 19 naive GBM tumor samples. RR cells generated from these cultures were characterized using various cell biological assays. We also collected clinicopathological data of the 19 patients and assessed associations with RR variables using Spearman's correlation test and with patient survival using Kaplan-Meier analysis. Significance was determined using a log-rank test. RESULTS: We found that SF2 (surviving fraction 2) values (p = 0.029), days of RR cell formation (p = 0.019) and percentage of giant cells (p = 0.034) in the RR population independently correlated with a poor patient survival. We also found that low ATM (Ataxia-telangiectasia mutated) expression levels in RR cells showed a significant (p = 0.002) negative correlation with SF2 values. A low ATM expression level in RR cells along with a high tumor volume was also found to negatively correlate with patient survival (p = 0.011). Finally, we found that the ATM expression levels in RR cells independently correlated with a poor patient survival (p = 0.014). CONCLUSIONS: Our data indicate that molecular features of innately radiation resistant GBM cells independently correlate with clinical outcome. Our study also highlights the relevance of using patient-derived primary GBM cultures for the characterization of RR cells that are otherwise inaccessible for analysis. FAU - Kaur, Ekjot AU - Kaur E AD - Shilpee Dutt Laboratory, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai, Maharashtra, 410210, India. AD - Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, Mumbai, 400085, India. FAU - Goda, Jayant S AU - Goda JS AD - Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, Mumbai, 400085, India. AD - Clinical Biology Lab, Department of Radiation Oncology, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Navi Mumbai, India. FAU - Ghorai, Atanu AU - Ghorai A AD - Shilpee Dutt Laboratory, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai, Maharashtra, 410210, India. AD - Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, Mumbai, 400085, India. FAU - Salunkhe, Sameer AU - Salunkhe S AD - Shilpee Dutt Laboratory, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai, Maharashtra, 410210, India. AD - Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, Mumbai, 400085, India. FAU - Shetty, Prakash AU - Shetty P AD - Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, Mumbai, 400085, India. AD - Department of Neurosurgery, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Navi Mumbai, India. FAU - Moiyadi, Aliasgar V AU - Moiyadi AV AD - Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, Mumbai, 400085, India. AD - Department of Neurosurgery, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Navi Mumbai, India. FAU - Sridhar, Epari AU - Sridhar E AD - Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, Mumbai, 400085, India. AD - Department of Pathology, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Navi Mumbai, India. FAU - Mahajan, Abhishek AU - Mahajan A AD - Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, Mumbai, 400085, India. AD - Clinical Biology Lab, Department of Radiation Oncology, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Navi Mumbai, India. FAU - Jalali, Rakesh AU - Jalali R AD - Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, Mumbai, 400085, India. AD - Clinical Biology Lab, Department of Radiation Oncology, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Navi Mumbai, India. FAU - Dutt, Shilpee AU - Dutt S AD - Shilpee Dutt Laboratory, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai, Maharashtra, 410210, India. sdutt@actrec.gov.in. AD - Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, Mumbai, 400085, India. sdutt@actrec.gov.in. LA - eng GR - BT/PR4020/MED/30/792/2012/Department of Biotechnology , Ministry of Science and Technology/ PT - Journal Article DEP - 20181026 PL - Netherlands TA - Cell Oncol (Dordr) JT - Cellular oncology (Dordrecht) JID - 101552938 SB - IM MH - Brain Neoplasms/*genetics/*radiotherapy/surgery MH - Cohort Studies MH - Glioblastoma/*genetics/*radiotherapy/surgery MH - Humans MH - Middle Aged MH - Neoplasm, Residual/*genetics MH - Radiation Tolerance/*genetics MH - Survival Analysis MH - Treatment Outcome OTO - NOTNLM OT - ATM OT - DNA repair OT - Glioblastoma OT - MNGCs OT - Patient-derived primary cultures OT - Radiation resistant cells EDAT- 2018/10/27 06:00 MHDA- 2019/05/28 06:00 CRDT- 2018/10/27 06:00 PHST- 2018/09/20 00:00 [accepted] PHST- 2018/10/27 06:00 [pubmed] PHST- 2019/05/28 06:00 [medline] PHST- 2018/10/27 06:00 [entrez] AID - 10.1007/s13402-018-0411-7 [pii] AID - 10.1007/s13402-018-0411-7 [doi] PST - ppublish SO - Cell Oncol (Dordr). 2019 Feb;42(1):107-116. doi: 10.1007/s13402-018-0411-7. Epub 2018 Oct 26.