Table 1.
Table summarizing the aspects highlighted in this review correlating with the key molecular events related with intratumoral heterogeneity
| Key points | Bibliography | |
|---|---|---|
| 1. Phenotypic heterogeneity | 1.1. Hundreds of tumor types and thousands of subtypes | Jamal-Hanjani et al. (2015) [1] |
| 1.2. Different degree of cell differentiation (low-grade and high-grade tumor types) | Park et al. (2010) [18] Zhou et al. (2015) [17] | |
| 1.3. Morphologic pattern association with genetic changes | Sequist et al. (2011) [22] Nielsen et al. (2015) [24] Zack et al. (2013) [26] | |
| 1.4. Morphological heterogeneity in metastasis vs. primary tumor | Maddipati et al. (2015) [50] Hong et al. (2015) [51] | |
| 2. Molecular heterogeneity | 2.1. Intratumor heterogeneity and resistance to treatments | Dagogo-Jack and Shaw (2018) [52] |
| 2.2. Different types of molecular changes in coding genes | JamalHanjani et al. (2017) [7] Sharma and Debinski (2018) [41] Karachaliou et al. (2015) [40] | |
| 2.2.1 SNV | ||
| 2.2.2 Insertions and Deletions | ||
| 2.2.3 Copy number variation | ||
| 2.2.4 Rearrangements (i.e translocations) | Skoulidis and Heymach (2019) [42] | |
| 2.3. Genomic Instability (CIN and MSI) | Dagogo-Jack and Shaw (2018) [52] Andor et al. (2016) [53] | |
| 2.4. Molecular and biochemical redundancy in the several pathways altered in malignant cells | Logue and Morrison (2012) [54] | |
| 2.5. Heterogeneity at genomic level is not always related with heterogeneity at proteomic level | Ramon Y Cajal S et al. (2017) [55] Ramon Y Cajal S et al. (2018) [56] | |
| 3. Epigenetic heterogeneity | 3.1 Different changes (histone modifications, DNA methylation) on the genome associated with gene silencing / gene activation | Kumar et al. (2018) [57] Dong et al. (2017) [58] Bhawal et al. (2007) [59] |
| 3.2. Deregulation of gene expression (overexpression or inhibition) | Agarwal R et al. (2017) [60] | |
| 3.2.1 conding genes: mRNAs | ||
| 3.2.2 non-coding RNAs: miRNAs, lncRNAs | Raychaudhuri et al. (2012) [33] Eriksen et al. (2016) [31] Ramon y Cajal et al.(2019) [34] | |
| 3.3. Associated and associated with the microenvironment | Assenov et al. (2018) [61] Yuan Y (2016) [62] |