Identification of candidate genes in a family with cancer overload by whole-exome sequencing

Hassani, Masoumeh; çelik, betül; KILIÇ ERCİYAS, Seda; TUNCER, SEREF BUGRA; Akdeniz Odemis, Demet; Büyükkapu Bay, Sema; SUKRUOGLU ERDOGAN, OZGE; Kebudi, Rejin; YAZICI, HÜLYA

doi:10.24953/turkjped.2021.4872

Identification of candidate genes in a family with cancer overload by whole-exome sequencing

Demet Akdeniz Odemis, (İstanbul Üniversitesi, Onkoloji Enstitüsü, Kanser Genetiği Anabilim Dalı, İstanbul, Türkiye)

Betül ÇELİK, (İstanbul Üniversitesi, Onkoloji Enstitüsü, Kanser Genetiği Anabilim Dalı, İstanbul, Türkiye)

ŞEREF BUĞRA TUNÇER, (İstanbul Üniversitesi, Onkoloji Enstitüsü, Kanser Genetiği Anabilim Dalı, İstanbul, Türkiye)

Seda KILIÇ ERCİYAS, (İstanbul Üniversitesi, Onkoloji Enstitüsü, Kanser Genetiği Anabilim Dalı, İstanbul, Türkiye)

OZGE SUKRUOGLU ERDOGAN, (İstanbul Üniversitesi, Onkoloji Enstitüsü, Kanser Genetiği Anabilim Dalı, İstanbul, Türkiye)

Hülya YAZICI, (İstanbul Üniversitesi, Onkoloji Enstitüsü, Kanser Genetiği Anabilim Dalı, İstanbul, Türkiye)

Rejin KEBUDİ, (İstanbul Üniversitesi, Onkoloji Enstitüsü, Çocuk Hematoloji-Onkoloji Anabilim Dalı, İstanbul, Türkiye)

Sema BÜYÜKKAPU BAY, (İstanbul Üniversitesi, Onkoloji Enstitüsü, Çocuk Hematoloji-Onkoloji Anabilim Dalı, İstanbul, Türkiye)

Masoumeh HASSANİ (İstanbul Gelişim Üniversitesi, Sağlık Hizmetleri Meslek Yüksekokulu, Patoloji Anabilim Dalı, Laboratuvar Teknikleri, İstanbul, Türkiye)

Turkish Journal of Pediatrics

1 0

Yıl: 2022 Cilt: 64 Sayı: 3 Sayfa Aralığı: 451 - 465 Metin Dili: İngilizce DOI: 10.24953/turkjped.2021.4872 İndeks Tarihi: 15-12-2022

Identification of candidate genes in a family with cancer overload by whole-exome sequencing

Öz:

Background. Approximately 120 out of every 1 million children in the world develop cancer each year. In Turkey, 2500-3000 children are diagnosed with new cancer each year. The causes of childhood cancer have been studied for many years. It is known that many cancers in children, as in adults, cause uncontrolled cell growth, and develop as a result of mutations in genes that cause cancer. Methods. The investigation of family history within this context in the study, a total of 13 individuals consisting of all children and adults in the family were examined using the whole-exome sequencing (WES) with the individuals who were diagnosed with cancer in the family, who were detected to have different cancer profiles, and defined as high risk and to determine the gene or genes through which the disease has developed. Results. At the end of the study, a total of 30 variants with a pathogenic record in the family were identified. A total of 10 pathogenic variants belonging to 8 different genes from these variants have been associated with various cancer risks. Conclusions. A significant scientific contribution has been made to the mechanism of disease formation by studying a family with a high cancer burden and by finding the genes associated with the disease. In addition, by the results obtained, family members with cancer predisposition were selected after a risk analysis conducted in this family, and the necessary examinations and scans were recommended to provide an early diagnostic advantage.

Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

1. Carrasco Salas P, Lapunzina P, Perez-Martinez A. Genetic predisposition to childhood cancer. An Pediatr (Barc) 2017; 87: 125-127. https://doi. org/10.1016/j.anpedi.2017.01.011
2. Vogelstein B, Kinzler KW. Cancer genes and the pathways they control. Nat Med 2004; 10: 789-799. https://doi.org/10.1038/nm1087
3. National Cancer Institute. Childhood cancers: Cancer in Children and Adolescents. 2017 [updated August 24, 2017]. Available from: https://www.cancer.gov/ types/childhood-cancers/child-adolescent-cancersfact- sheet
4. Ries LAG, Smith MA, Gurney JG, Linet M, Tamra T, Young JL, Bunin GR (editors). Cancer incidence and survival among children and adolescents: United States SEER Program 1975-1995. NIH Pub. No. 99-4649. 1999. Available from: https://seer.cancer. gov/archive/publications/childhood/childhoodmonograph. pdf
5. MacDonald T. Pediatric cancer: A comprehensive review. Part I: Biology, epidemiology, common tumours, principles of treatment and late effects. Can Pharm J 2010; 143: 176-183. https://doi. org/10.3821/1913-701X-143.4.176
6. Malkin D. Li-fraumeni syndrome. Genes Cancer 2011; 2: 475-484. https://doi.org/10.1177/1947601911413466
7. Seif AE. Pediatric leukemia predisposition syndromes: clues to understanding leukemogenesis. Cancer Genet 2011; 204: 227-244. https://doi. org/10.1016/j.cancergen.2011.04.005
8. Ross JA, Spector LG, Robison LL, Olshan AF. Epidemiology of leukemia in children with Down syndrome. Pediatr Blood Cancer 2005; 44: 8-12. https://doi.org/10.1002/pbc.20165
9. DeBaun MR, Tucker MA. Risk of cancer during the first four years of life in children from The Beckwith-Wiedemann Syndrome Registry. J Pediatr 1998; 132: 398-400. https://doi.org/10.1016/S0022- 3476(98)70008-3
10. Choong SS, Latiff ZA, Mohamed M, et al. Childhood adrenocortical carcinoma as a sentinel cancer for detecting families with germline TP53 mutations. Clin Genet 2012; 82: 564-568. https://doi.org/10.1111/ j.1399-0004.2012.01841.x
11. Nagy R, Sweet K, Eng C. Highly penetrant hereditary cancer syndromes. Oncogene 2004; 23: 6445-6470. https://doi.org/10.1038/sj.onc.1207714
12. Stoppa-Lyonnet D, Houdayer C. New generation sequencing in medical genetics. Med Sci (Paris) 2012; 28: 123-124. https://doi.org/10.1051/ medsci/2012282001
13. Zhang J, Walsh MF, Wu G, et al. Germline mutations in predisposition genes in pediatric cancer. N Engl J Med 2015; 373: 2336-2346. https://doi.org/10.1056/ NEJMoa1508054
14. Molnar L, Leibinger J, Balo-Banga JM, Racz I. A rapid centrifugation method for the isolation of polymorphonuclear leucocytes from human blood. Acta Physiol Acad Sci Hung 1981; 57: 255-260. PMID: 6171135.
15. Ip SC, Lin SW, Lai KM. An evaluation of the performance of five extraction methods: Chelex(R) 100, QIAamp(R) DNA Blood Mini Kit, QIAamp(R) DNA Investigator Kit, QIAsymphony(R) DNA Investigator(R) Kit and DNA IQ. Sci Justice 2015; 55: 200-208. https://doi.org/10.1016/j.scijus.2015.01.005
16. Liang WS, Stephenson K, Adkins J, et al. Whole exome library construction for next generation sequencing. Methods Mol Biol 2018; 1706: 163-174. https://doi.org/10.1007/978-1-4939-7471-9_9
17. Li Q, Lin Y. Evaluation of Ficolin-3 as a potential prognostic serum biomarker in chinese patients with esophageal cancer. Genet Test Mol Biomarkers 2019; 23: 565-572. https://doi.org/10.1089/gtmb.2019.0045
18. Garred P, Honore C, Ma YJ, et al. The genetics of ficolins. J Innate Immun 2010; 2: 3-16. https://doi. org/10.1159/000242419
19. Andersen JD, Boylan KL, Xue FS, et al. Identification of candidate biomarkers in ovarian cancer serum by depletion of highly abundant proteins and differential in-gel electrophoresis. Electrophoresis 2010; 31: 599-610. https://doi.org/10.1002/ elps.200900441
20. Byrne JC, Downes MR, O’Donoghue N, et al. 2D-DIGE as a strategy to identify serum markers for the progression of prostate cancer. J Proteome Res 2009; 8: 942-957. https://doi.org/10.1021/pr800570s
21. Braoudaki M, Lambrou GI, Vougas K, Karamolegou K, Tsangaris GT, Tzortzatou-Stathopoulou F. Protein biomarkers distinguish between high- and low-risk pediatric acute lymphoblastic leukemia in a tissue specific manner. J Hematol Oncol 2013; 6: 52-72. https://doi.org/10.1186/1756-8722-6-52
22. Schlapbach LJ, Aebi C, Hansen AG, Hirt A, Jensenius JC, Ammann RA. H-ficolin serum concentration and susceptibility to fever and neutropenia in paediatric cancer patients. Clin Exp Immunol 2009; 157: 83-89. https://doi.org/10.1111/j.1365-2249.2009.03957.x
23. Walport MJ. Complement. First of two parts. N Engl J Med 2001; 344: 1058-1066. https://doi.org/10.1056/ NEJM200104053441406
24. Chung DW, Fujikawa K, McMullen BA, Davie EW. Human plasma prekallikrein, a zymogen to a serine protease that contains four tandem repeats. Biochemistry 1986; 25: 2410-2417. https://doi. org/10.1021/bi00357a017
25. Barco S, Sollfrank S, Trinchero A, et al. Severe plasma prekallikrein deficiency: Clinical characteristics, novel KLKB1 mutations, and estimated prevalence. J Thromb Haemost 2020; 18: 1598-1617. https://doi. org/10.1111/jth.14805
26. Wong J, Sia YY, Misso NL, Aggarwal S, Ng A, Bhoola KD. Effects of the demethylating agent, 5-azacytidine, on expression of the kallikrein-kinin genes in carcinoma cells of the lung and pleura. Patholog Res Int 2011; 2011: 1670-1681. https://doi. org/10.4061/2011/167046
27. Hasegawa T, Lewis H, Esquela-Kerscher A. Chapter 12 - The Role of Noncoding RNAs in Prostate Cancer. In: Laurence J, editor. Translating MicroRNAs to the Clinic. Boston: Academic Press; 2017. p. 329-369. https://doi.org/10.1016/B978-0-12-800553-8.00012-3
28. Hou YC, Yu HC, Martin R, et al. Precision medicine integrating whole-genome sequencing, comprehensive metabolomics, and advanced imaging. Proc Natl Acad Sci U S A 2020; 117: 3053- 3062. https://doi.org/10.1073/pnas.1909378117
29. Fernie BA, Wurzner R, Orren A, et al. Molecular bases of combined subtotal deficiencies of C6 and C7: their effects in combination with other C6 and C7 deficiencies. J Immunol 1996; 157: 3648-3657.
30. Coussens LM, Werb Z. Inflammation and cancer. Nature 2002; 420: 860-867. https://doi.org/10.1038/ nature01322
31. Carroll MC, Isenman DE. Regulation of humoral immunity by complement. Immunity 2012; 37: 199- 207. https://doi.org/10.1016/j.immuni.2012.08.002
32. Afshar-Kharghan V. The role of the complement system in cancer. J Clin Invest 2017; 127: 780-789. https://doi.org/10.1172/JCI90962
33. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011; 144: 646-674. https://doi. org/10.1016/j.cell.2011.02.013
34. Bonavita E, Gentile S, Rubino M, et al. PTX3 is an extrinsic oncosuppressor regulating complementdependent inflammation in cancer. Cell 2015; 160: 700-714. https://doi.org/10.1016/j.cell.2015.01.004
35. Parkes M, Barrett JC, Prescott NJ, et al. Sequence variants in the autophagy gene IRGM and multiple other replicating loci contribute to Crohn’s disease susceptibility. Nat Genet 2007; 39: 830-832. https:// doi.org/10.1038/ng2061
36. Song JH, Kim SY, Chung KS, et al. Association between genetic variants in the IRGM gene and tuberculosis in a Korean population. Infection 2014; 42: 655-660. https://doi.org/10.1007/s15010-014-0604- 6
37. Singh SB, Davis AS, Taylor GA, Deretic V. Human IRGM induces autophagy to eliminate intracellular mycobacteria. Science 2006; 313: 1438-1441. https:// doi.org/10.1126/science.1129577
38. Crotzer VL, Blum JS. Autophagy and adaptive immunity. Immunology 2010; 131: 9-17. https://doi. org/10.1111/j.1365-2567.2010.03321.x
39. Virgin HW, Levine B. Autophagy genes in immunity. Nat Immunol 2009; 10: 461-470. https:// doi.org/10.1038/ni.1726
40. Yao QM, Zhu YF, Wang W, et al. Polymorphisms in autophagy-related gene IRGM are associated with susceptibility to autoimmune thyroid diseases. Biomed Res Int 2018; 2018: 1-7. https://doi. org/10.1155/2018/7959707
41. Burada F, Plantinga TS, Ioana M, et al. IRGM gene polymorphisms and risk of gastric cancer. J Dig Dis 2012; 13: 360-365. https://doi.org/10.1111/j.1751- 2980.2012.00602.x
42. Song Z, Guo C, Zhu L, et al. Elevated expression of immunity-related GTPase family M in gastric cancer. Tumour Biol 2015; 36: 5591-5596. https://doi. org/10.1007/s13277-015-3229-1
43. Zou WB, Tang XY, Zhou DZ, et al. SPINK1, PRSS1, CTRC, and CFTR genotypes influence disease onset and clinical outcomes in chronic pancreatitis. Clin Transl Gastroenterol 2018; 9: 204-216. https://doi. org/10.1038/s41424-018-0069-5
44. Bouwman LH, Roep BO, Roos A. Mannosebinding lectin: clinical implications for infection, transplantation, and autoimmunity. Hum Immunol 2006; 67: 247-256. https://doi.org/10.1016/j. humimm.2006.02.030
45. Eisen DP, Minchinton RM. Impact of mannosebinding lectin on susceptibility to infectious diseases. Clin Infect Dis 2003; 37: 1496-1505. https:// doi.org/10.1086/379324
46. Peterslund NA, Koch C, Jensenius JC, Thiel S. Association between deficiency of mannose-binding lectin and severe infections after chemotherapy. Lancet 2001; 358: 637-638. https://doi.org/10.1016/ S0140-6736(01)05785-3
47. Rutkowski MJ, Sughrue ME, Kane AJ, Mills SA, Parsa AT. Cancer and the complement cascade. Mol Cancer Res 2010; 8: 1453-1465. https://doi. org/10.1158/1541-7786.MCR-10-0225
48. Bernig T, Boersma BJ, Howe TM, et al. The mannosebinding lectin (MBL2) haplotype and breast cancer: an association study in African-American and Caucasian women. Carcinogenesis 2007; 28: 828-836. https://doi.org/10.1093/carcin/bgl198
49. Baccarelli A, Hou L, Chen J, et al. Mannose-binding lectin-2 genetic variation and stomach cancer risk. Int J Cancer 2006; 119: 1970-1975. https://doi. org/10.1002/ijc.22075
50. Wang FY, Tahara T, Arisawa T, et al. Mannan-binding lectin (MBL) polymorphism and gastric cancer risk in Japanese population. Dig Dis Sci 2008; 53: 2904- 2908. https://doi.org/10.1007/s10620-008-0249-3
51. Zanetti KA, Haznadar M, Welsh JA, et al. 3’-UTR and functional secretor haplotypes in mannosebinding lectin 2 are associated with increased colon cancer risk in African Americans. Cancer Res 2012; 72: 1467-1477. https://doi.org/10.1158/0008-5472. CAN-11-3073
52. Segat L, Crovella S, Comar M, et al. MBL2 gene polymorphisms are correlated with high-risk human papillomavirus infection but not with human papillomavirus-related cervical cancer. Hum Immunol 2009; 70: 436-439. https://doi.org/10.1016/j. humimm.2009.03.006
53. Pine SR, Mechanic LE, Ambs S, et al. Lung cancer survival and functional polymorphisms in MBL2, an innate-immunity gene. J Natl Cancer Inst 2007; 99: 1401-1409. https://doi.org/10.1093/jnci/djm128
54. Ytting H, Christensen IJ, Steffensen R, et al. Mannanbinding lectin (MBL) and MBL-associated serine protease 2 (MASP-2) genotypes in colorectal cancer. Scand J Immunol 2011; 73: 122-127. https://doi. org/10.1111/j.1365-3083.2010.02480.x
55. Toland AE, Rozek LS, Presswala S, Rennert G, Gruber SB. PTPRJ haplotypes and colorectal cancer risk. Cancer Epidemiol Biomarkers Prev 2008; 17: 2782-2785. https://doi.org/10.1158/1055-9965.EPI-08- 0513
56. Ruivenkamp CA, van Wezel T, Zanon C, et al. Ptprj is a candidate for the mouse colon-cancer susceptibility locus Scc1 and is frequently deleted in human cancers. Nat Genet 2002; 31: 295-300. https:// doi.org/10.1038/ng903
57. Iuliano R, Le Pera I, Cristofaro C, et al. The tyrosine phosphatase PTPRJ/DEP-1 genotype affects thyroid carcinogenesis. Oncogene 2004; 23: 8432-8438. https://doi.org/10.1038/sj.onc.1207766
58. Lesueur F, Pharoah PD, Laing S, et al. Allelic association of the human homologue of the mouse modifier Ptprj with breast cancer. Hum Mol Genet 2005; 14: 2349-2356. https://doi.org/10.1093/hmg/ ddi237
59. Plaitakis A, Latsoudis H, Kanavouras K, et al. Gain-of-function variant in GLUD2 glutamate dehydrogenase modifies Parkinson’s disease onset. Eur J Hum Genet 2010; 18: 336-341. https://doi. org/10.1038/ejhg.2009.179
60. Akdeniz Odemis D, Tuncer SB, Adamnejad Ghafour A, et al. FGFR4 c.1162G > A (p.Gly388Arg) polymorphism analysis in Turkish patients with retinoblastoma. J Oncol 2020; 2020: 9401-9409. https://doi.org/10.1155/2020/9401038
61. Bange J, Prechtl D, Cheburkin Y, et al. Cancer progression and tumor cell motility are associated with the FGFR4 Arg(388) allele. Cancer Res 2002; 62: 840-847. PMID: 11830541.
62. Leung HY, Gullick WJ, Lemoine NR. Expression and functional activity of fibroblast growth factors and their receptors in human pancreatic cancer. Int J Cancer 1994; 59: 667-675. https://doi.org/10.1002/ ijc.2910590515
63. Wang J, Stockton DW, Ittmann M. The fibroblast growth factor receptor-4 Arg388 allele is associated with prostate cancer initiation and progression. Clin Cancer Res 2004; 10: 6169-6178. https://doi. org/10.1158/1078-0432.CCR-04-0408
64. Brito LP, Lerario AM, Bronstein MD, Soares IC, Mendonca BB, Fragoso MC. Influence of the fibroblast growth factor receptor 4 expression and the G388R functional polymorphism on Cushing’s disease outcome. J Clin Endocrinol Metab 2010; 95: 271-279. https://doi.org/10.1210/jc.2010-0047
65. Akdeniz D, Tuncer SB, Kebudi R, et al. Investigation of new candidate genes in retinoblastoma using the TruSight One “clinical exome” gene panel. Mol Genet Genomic Med 2019; 7: 785-799. https://doi. org/10.1002/mgg3.785
66. Butler JM, Sharif U, Ali M, et al. A missense variant in CST3 exerts a recessive effect on susceptibility to age-related macular degeneration resembling its association with Alzheimer’s disease. Hum Genet 2015; 134: 705-715. https://doi.org/10.1007/s00439- 015-1552-7
67. Migita K, Agematsu K, Masumoto J, et al. The contribution of SAA1 polymorphisms to Familial Mediterranean fever susceptibility in the Japanese population. PLoS One 2013; 8: 55227-55234. https:// doi.org/10.1371/journal.pone.0055227
68. Kim JG, Sohn SK, Chae YS, et al. TP53 codon 72 polymorphism associated with prognosis in patients with advanced gastric cancer treated with paclitaxel and cisplatin. Cancer Chemother Pharmacol 2009; 64: 355-360. https://doi.org/10.1007/s00280-008-0879- 3
69. Khrunin AV, Moisseev A, Gorbunova V, Limborska S. Genetic polymorphisms and the efficacy and toxicity of cisplatin-based chemotherapy in ovarian cancer patients. Pharmacogenomics J 2010; 10: 54-61. https://doi.org/10.1038/tpj.2009.45
70. Henriquez-Hernandez LA, Murias-Rosales A, Gonzalez-Hernandez A, de Leon AC, Diaz-Chico N, Fernandez-Perez L. Distribution of TYMS, MTHFR, p53 and MDR1 gene polymorphisms in patients with breast cancer treated with neoadjuvant chemotherapy. Cancer Epidemiol 2010; 34: 634-638. https://doi.org/10.1016/j.canep.2010.06.013

APA	Akdeniz Odemis D, çelik b, TUNCER S, KILIÇ ERCİYAS S, SUKRUOGLU ERDOGAN O, YAZICI H, Kebudi R, Büyükkapu Bay S, Hassani M (2022). Identification of candidate genes in a family with cancer overload by whole-exome sequencing. , 451 - 465. 10.24953/turkjped.2021.4872
Chicago	Akdeniz Odemis Demet,çelik betül,TUNCER SEREF BUGRA,KILIÇ ERCİYAS Seda,SUKRUOGLU ERDOGAN OZGE,YAZICI HÜLYA,Kebudi Rejin,Büyükkapu Bay Sema,Hassani Masoumeh Identification of candidate genes in a family with cancer overload by whole-exome sequencing. (2022): 451 - 465. 10.24953/turkjped.2021.4872
MLA	Akdeniz Odemis Demet,çelik betül,TUNCER SEREF BUGRA,KILIÇ ERCİYAS Seda,SUKRUOGLU ERDOGAN OZGE,YAZICI HÜLYA,Kebudi Rejin,Büyükkapu Bay Sema,Hassani Masoumeh Identification of candidate genes in a family with cancer overload by whole-exome sequencing. , 2022, ss.451 - 465. 10.24953/turkjped.2021.4872
AMA	Akdeniz Odemis D,çelik b,TUNCER S,KILIÇ ERCİYAS S,SUKRUOGLU ERDOGAN O,YAZICI H,Kebudi R,Büyükkapu Bay S,Hassani M Identification of candidate genes in a family with cancer overload by whole-exome sequencing. . 2022; 451 - 465. 10.24953/turkjped.2021.4872
Vancouver	Akdeniz Odemis D,çelik b,TUNCER S,KILIÇ ERCİYAS S,SUKRUOGLU ERDOGAN O,YAZICI H,Kebudi R,Büyükkapu Bay S,Hassani M Identification of candidate genes in a family with cancer overload by whole-exome sequencing. . 2022; 451 - 465. 10.24953/turkjped.2021.4872
IEEE	Akdeniz Odemis D,çelik b,TUNCER S,KILIÇ ERCİYAS S,SUKRUOGLU ERDOGAN O,YAZICI H,Kebudi R,Büyükkapu Bay S,Hassani M "Identification of candidate genes in a family with cancer overload by whole-exome sequencing." , ss.451 - 465, 2022. 10.24953/turkjped.2021.4872
ISNAD	Akdeniz Odemis, Demet vd. "Identification of candidate genes in a family with cancer overload by whole-exome sequencing". (2022), 451-465. https://doi.org/10.24953/turkjped.2021.4872

APA	Akdeniz Odemis D, çelik b, TUNCER S, KILIÇ ERCİYAS S, SUKRUOGLU ERDOGAN O, YAZICI H, Kebudi R, Büyükkapu Bay S, Hassani M (2022). Identification of candidate genes in a family with cancer overload by whole-exome sequencing. Turkish Journal of Pediatrics, 64(3), 451 - 465. 10.24953/turkjped.2021.4872
Chicago	Akdeniz Odemis Demet,çelik betül,TUNCER SEREF BUGRA,KILIÇ ERCİYAS Seda,SUKRUOGLU ERDOGAN OZGE,YAZICI HÜLYA,Kebudi Rejin,Büyükkapu Bay Sema,Hassani Masoumeh Identification of candidate genes in a family with cancer overload by whole-exome sequencing. Turkish Journal of Pediatrics 64, no.3 (2022): 451 - 465. 10.24953/turkjped.2021.4872
MLA	Akdeniz Odemis Demet,çelik betül,TUNCER SEREF BUGRA,KILIÇ ERCİYAS Seda,SUKRUOGLU ERDOGAN OZGE,YAZICI HÜLYA,Kebudi Rejin,Büyükkapu Bay Sema,Hassani Masoumeh Identification of candidate genes in a family with cancer overload by whole-exome sequencing. Turkish Journal of Pediatrics, vol.64, no.3, 2022, ss.451 - 465. 10.24953/turkjped.2021.4872
AMA	Akdeniz Odemis D,çelik b,TUNCER S,KILIÇ ERCİYAS S,SUKRUOGLU ERDOGAN O,YAZICI H,Kebudi R,Büyükkapu Bay S,Hassani M Identification of candidate genes in a family with cancer overload by whole-exome sequencing. Turkish Journal of Pediatrics. 2022; 64(3): 451 - 465. 10.24953/turkjped.2021.4872
Vancouver	Akdeniz Odemis D,çelik b,TUNCER S,KILIÇ ERCİYAS S,SUKRUOGLU ERDOGAN O,YAZICI H,Kebudi R,Büyükkapu Bay S,Hassani M Identification of candidate genes in a family with cancer overload by whole-exome sequencing. Turkish Journal of Pediatrics. 2022; 64(3): 451 - 465. 10.24953/turkjped.2021.4872
IEEE	Akdeniz Odemis D,çelik b,TUNCER S,KILIÇ ERCİYAS S,SUKRUOGLU ERDOGAN O,YAZICI H,Kebudi R,Büyükkapu Bay S,Hassani M "Identification of candidate genes in a family with cancer overload by whole-exome sequencing." Turkish Journal of Pediatrics, 64, ss.451 - 465, 2022. 10.24953/turkjped.2021.4872
ISNAD	Akdeniz Odemis, Demet vd. "Identification of candidate genes in a family with cancer overload by whole-exome sequencing". Turkish Journal of Pediatrics 64/3 (2022), 451-465. https://doi.org/10.24953/turkjped.2021.4872