Loss of heterozygosity of key tumor suppressor genes in advanced renal cancer patients treated with nivolumab

被引：3
作者：
Bersanelli, Melissa [1 ]
Gnetti, Letizia [2 ]
Azzoni, Cinzia [2 ]
Bottarelli, Lorena [2 ]
Sverzellati, Nicola [3 ]
Campanini, Nicoletta [2 ]
Varotti, Elena [2 ]
Corrado, Michele [3 ]
Parziale, Raffaele [3 ]
Rapacchi, Elena [1 ]
Caruso, Giuseppe [1 ]
Leonardi, Francesco [1 ]
Silini, Enrico Maria [2 ]
Buti, Sebastiano [1 ]
机构：
[1] Univ Hosp Parma, Med Oncol, Via Gramsci 14, I-43126 Parma, Italy
[2] Univ Hosp Parma, Pathol Anat Unit, Via Gramsci 14, I-43126 Parma, Italy
[3] Univ Hosp Parma, Radiol Unit, Via Gramsci 14, I-43126 Parma, Italy
来源：
IMMUNOTHERAPY | 2018年 / 10卷 / 09期
关键词：
FHIT; loss of heterozygosity; renal cell carcinoma; SPORADIC BREAST-CANCER; CLEAR-CELL CARCINOMA; MISMATCH-REPAIR; MICROSATELLITE INSTABILITY; OVARIAN-CANCER; BRCA2; VHL; 3P; TUMORIGENESIS; GUIDELINES;
D O I：
10.2217/imt-2017-0160
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
Aim: We studied the possible clinical significance of loss of heterozygosity (LOH) at key tumor suppressor genes loci in advanced renal cancer patients treated with nivolumab. Methods: LOH study was performed on 3p14.2 (FHIT gene); 3p21.3-21.2; 9p21 (BDMF gene); 9p22 (SH3GL2 gene). Results: Of 12 patients, 8 (67%) had LOH. The most affected gene was FHIT. All five patients with LOH at FHIT locus had good outcome, mean progression free survival of 6.8 months. The patients LOH negative at FHIT locus had mean progression free survival of 4 months, 67% were treatment refractory. Overall, 75% of patients with LOH of at least one gene had benefit; 75% of LOH negative cases were refractory. Conclusion: LOH at key tumor suppressor genes should be further investigated as predictive for immunotherapy.
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页码：743 / +
页数：11
相关论文
共 31 条
  • [11] Giordano A, 2010, CANC EPIGENETICS
  • [12] Hanby AM, 2000, INT J CANCER, V88, P204
  • [13] CTLA-4 Blockade Synergizes Therapeutically with PARP Inhibition in BRCA1-Deficient Ovarian Cancer
    Higuchi, Tomoe
    Flies, Dallas B.
    Marjon, Nicole A.
    Mantia-Smaldone, Gina
    Ronner, Lukas
    Gimotty, Phyllis A.
    Adams, Sarah F.
    [J]. CANCER IMMUNOLOGY RESEARCH, 2015, 3 (11) : 1257 - 1268
  • [14] MOLECULAR ORIGINS OF CANCER DNA Damage, Aging, and Cancer
    Hoeijmakers, Jan H. J.
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2009, 361 (15) : 1475 - 1485
  • [15] Frequent Mutations of Chromatin Remodeling Gene ARID1A in Ovarian Clear Cell Carcinoma
    Jones, Sian
    Wang, Tian-Li
    Shih, Ie-Ming
    Mao, Tsui-Lien
    Nakayama, Kentaro
    Roden, Richard
    Glas, Ruth
    Slamon, Dennis
    Diaz, Luis A., Jr.
    Vogelstein, Bert
    Kinzler, Kenneth W.
    Velculescu, Victor E.
    Papadopoulos, Nickolas
    [J]. SCIENCE, 2010, 330 (6001) : 228 - 231
  • [16] Cell-cycle checkpoints and cancer
    Kastan, MB
    Bartek, J
    [J]. NATURE, 2004, 432 (7015) : 316 - 323
  • [17] Mismatch Repair-Deficient Cancers Are Targets for Anti-PD-1 Therapy
    Kelderman, Sander
    Schumacher, Ton N.
    Kvistborg, Pia
    [J]. CANCER CELL, 2015, 28 (01) : 11 - 13
  • [18] PD-1 Blockade in Tumors with Mismatch-Repair Deficiency
    Le, D. T.
    Uram, J. N.
    Wang, H.
    Bartlett, B. R.
    Kemberling, H.
    Eyring, A. D.
    Skora, A. D.
    Luber, B. S.
    Azad, N. S.
    Laheru, D.
    Biedrzycki, B.
    Donehower, R. C.
    Zaheer, A.
    Fisher, G. A.
    Crocenzi, T. S.
    Lee, J. J.
    Duffy, S. M.
    Goldberg, R. M.
    de la Chapelle, A.
    Koshiji, M.
    Bhaijee, F.
    Huebner, T.
    Hruban, R. H.
    Wood, L. D.
    Cuka, N.
    Pardoll, D. M.
    Papadopoulos, N.
    Kinzler, K. W.
    Zhou, S.
    Cornish, T. C.
    Taube, J. M.
    Anders, R. A.
    Eshleman, J. R.
    Vogelstein, B.
    Diaz, L. A., Jr.
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2015, 372 (26) : 2509 - 2520
  • [19] DNA damage, tumor mutational load and their impact on immune responses against cancer
    Liontos, Michalis
    Anastasiou, Ioannis
    Bamias, Aristotelis
    Dimopoulos, Meletios-Athanasios
    [J]. ANNALS OF TRANSLATIONAL MEDICINE, 2016, 4 (14)
  • [20] Role of chromosome 3p12-p21 tumour suppressor genes in clear cell renal cell carcinoma: analysis of VHL dependent and VHL independent pathways of tumorigenesis
    Martinez, A
    Fullwood, P
    Kondo, K
    Kishida, T
    Yao, M
    Maher, ER
    Latif, F
    [J]. JOURNAL OF CLINICAL PATHOLOGY-MOLECULAR PATHOLOGY, 2000, 53 (03): : 137 - 144
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