ZNAČAJ MOLEKULARNE GENETIKE ZA SKRINING KANCERA
Sažetak
Uprkos napretku medicine, kancer je i dalje jedan od glavnih uzroka smrti u svetu. Ovo je pre svega posledica odsustva simptoma u toku progresije tumora, tako da je često u trenutku pojave simptoma bolest već u fazi kada je lečenje nemoguće. Zbog toga je razvoj specifičnih i senzitivnih metoda koje će omogućiti ranu detekciju tumora od izuzetne važnosti. Unapređenje postojećih i razvoj novih metoda molekularne genetike, uz snižavanje cene analiza, moglo bi predstavljati rešenje ovog problema. Prilikom razvoja metoda za ranu detekciju tumora treba praviti razliku da li je metoda namenjena detekciji naslednih kancerskih sindroma ili sporadičnih tumora. U slučaju naslednih kancerskih sindroma, molekularno genetičke metode se koriste da bi se detektovalo prisustvo germinativne mutacije gena za koju je poznato da je odgovorna za nastanak datog naslednog kancerskog sindroma, u cilju određivanje predispozicije za obolevanje pacijenta koji je član porodice pod rizikom. Mutacija je prisutna u svim ćelijama organizma, pa se može detektovati analizom DNK izolovane iz telesnih tečnosti ili bukalne sluzokože. Nasuprot ovome, kod sporadičnih tumora je neophodan skrining zdrave populacije u odsustvu bilo kakvih informacija o lokalizaciji tumora ili genetičkim promenama. Metodu izbora u ovom slučaju bi mogle predstavljati tečne biopsije, gde se molekularno genetičkim metodama analiziraju promene u genetičkom materijalu prisutnom u telesnim tečnostima ispitanika. Ovom metodom se tumor kod pacijenta otkriva, na primer, na osnovu promene u koncentraciji slobodne cirkulišuće DNK u krvi (cfDNA) ili na osnovu prisustva cirkulišuće tumorske DNK (ctDNA). Takođe, u skriningu za kancer se, pored genetičkih, moraju uzeti u obzir i epigenetičke promene.
Reference
Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014; 64: 9-29.
World Health Organisation [Internet] [cited 2020 June 12]. Available at: https://www.who.int/cancer/ prevention/en/
Mattox AK, Bettegowda C, Zhou S, Papadopoulos N, Kinzler KW, Vogelstein B. Applications of Liquid Biopsies for Cancer. Sci Transl Med 2019; 11(507):eaay1984.
Rahner N, Steinke V, Hereditary Cancer Syndromes. Dtsch Arztebl Int 2008; 105(41): 706–714.
Atlas of Genetics and Cytogenetics in Oncology and Haematology [Internet], Kaija Holli: Hereditary breast cancer [cited 2020 June 12]. Available at: http://atlasgeneticsoncology.org/Kprones/ HeredBreastCanID10062.html
Deng CX. BRCA1: cell cycle checkpoint, genetic instability, DNA damage response and cancer evolution. Nucleic Acids Res 2006; 34:1416–26.
Antoniou AC, Pharoah PD, McMullan G, Day NE, Ponder BA, Easton D. Evidence for further breast cancer susceptibility genes in addition to BRCA1 and BRCA2 in a population-based study. Genet Epidemiol 2001; 21:1–18.
Walsh T, Casadei S, Coats KH. Spectrum of mutations in BRCA1, BRCA2, CHEK2, and TP53 in families at high risk of breast cancer. JAMA 2006;295(22):1379– 1388.
Cavanagh H, Rogers KMA. The role of BRCA1 and BRCA2 mutations in prostate, pancreatic and stomach cancers. Hered Cancer Clin Pract 2015;13: 16.
Lamberti C, Mangold E, Pagenstecher C, Jungck M, Schwering D, Bollmann M, et al. Frequency of hereditary non-polyposis colorectal cancer among unselected patients with colorectal cancer in Germany. Digestion 2006; 74:58–67.
Lynch HT, de la Chapelle A. Hereditary colorectal cancer. N Engl J Med 2003; 348:919–932.
Parsons DW, Jones S, Zhang X, Cheng Ho-Lin J, Leary RJ, Angenendt P, et al. An Integrated Genomic Analysis of Human Glioblastoma Multiforme. Science 2008; 321:1807-12.
Boesch M, Zeimet AG, Reimer D, Schmidt S, Gastl G, et al. The side population of ovarian cancer cells defines a heterogeneous compartment exhibiting stem cell characteristics. Oncotarget 2014; 5: 7027-39.
National Cancer Institute. NCI Dictionary of Cancer Terms. Available from: https://www.cancer.gov/publications/dictionaries/cancer-terms
Castro D, Moreira M, Gouveia AM, et al. MicroRNAs in lung cancer. Oncotarget 2017; 8: 81679-85.
Sozzi G, Boeri M, Rossi M, Verri C, Suatoni P, Bravi F, et al. Clinical Utility of a Plasma-Based miRNA Signature Classifier Within Computed Tomography Lung Cancer Screening: A Correlative MILD Trial Study. J Clin Oncol 2014; 32: 768-73.
Adams DL, Adams DK, Alpaugh RK, Cristofanilli M, Martin SS, Chumsri S, et al. Circulating Cancer- Associated Macrophage-Like Cells Differentiate Malignant Breast Cancer and Benign Breast Conditions. Cancer Epidemiol Biomarkers Prev 2016; 25: 1037-42.
Catarino R, Coelho A, Araujo A, Gomes M, Nogueir A, Lopes C, et al. Circulating DNA: Diagnostic Tool and Predictive Marker for Overall Survival of NSCLC Patients. PLoS One 2012; 7: e38559.
Lin Z, Neiswender J, Fang B, Ma X, Zhan J, HuX,et al. Value of circulating cell-free DNA analysis as a diagnostic tool for breast cancer: a meta-analysis. Oncotarget 2017; 8: 26625-36.
Zhou Q, Li W, Leng B, Zheng W, He Z, Zuo M, Chen A, et al. Circulating Cell Free DNA as the Diagnostic Marker for Ovarian Cancer: A Systematic Review and Meta-Analysis. PLoS One 2016; 11: e0155495.
Schwarzenbach H, Hoon DS, Pantel K. Cell-free nucleic acids as biomarkers in cancer patients. Nat Rev Cancer 2011; 11: 426-37.
Mouliere F, El Messaoudi S, Pang D, Dritschilo A, Thierry AR. Multi-marker analysis of circulating cell-free DNA toward personalized medicine for colorectal cancer. Mol Oncol 2014; 8: 927-41.
Best MG, Sol N, Kooi I, Tannous J, Westerman BA, Rustenburg F, et al. RNA-Seq of Tumor-Educated Platelets Enables Blood-Based Pan-Cancer, Multiclass, and Molecular Pathway Cancer Diagnostics. Cancer Cell 2015; 28: 666-76.
Underhill HR, Kitzman JO, Hellwig S, Welker NC, Daza R, Baker DN, et al. Fragment length of circulating tumor DNA. PLoS Genet 2016; 12: e1006162.
Mouliere F, Robert B, Peyrotte EA, Rio MD, Ychou M, Molina F, et al. High Fragmentation Characterizes Tumour-Derived Circulating DNA. PLoS One 2011; 6: e23418.
Tóth K, Wasserkort R, Sipos F, Kalmar M, Wichmann B. Leiszter K, et al. Detection of Methylated Septin 9 in Tissue and Plasma of Colorectal Patients with Neoplasia and the Relationship to the Amount of Circulating Cell-Free DNA. PLoS One 2014; 9: e115415.