The idea that common epithelial cancers evolve from dysplasia or carcinoma in situ has been challenged by the discovery of occult disease in normal-appearing cells, known as the field effect, which interests areas that might form large plaques in the mucosal membrane. Forerunner (FR) genes, which map to genomic regions close to established tumour-suppressor genes, seem to have a role in this process, as inactivation of FR genes precedes the functional loss of the close tumour suppressors.

In a new study published in Cell Reports, the authors developed an innovative whole-organ mapping method that, in combination with genomic markers, can help dissect the sequence of events of initial clonal expansion of a preneoplastic clone. This strategy was used to identify FR genes in the region around the tumour suppressor RB1. A minimal segment of 1.7 Mb whose loss of polymorphisms was associated with early clonal expansion of a preneoplastic clone was identified and included 20 putative candidate genes. Expression studies on a 5-Mb segment around RB1 enabled the identification of five FR genes whose expression was downregulated by at least twofold in >50% of the samples: ITM2B, LPAR6, MLNR, CAB39L and ARL11. Hypermethylation was identified as the primary mechanism of silencing of these genes.

常见上皮癌是由不典型增生或原位癌演变而来的观点受到了在正常细胞中发现的隐匿性疾病的挑战，这种疾病被称为场效应，它关注的是可能在粘膜中形成大斑块的区域。先行者 (FR) 基因映射到靠近已建立的肿瘤抑制基因的基因组区域，似乎在这一过程中发挥着作用，因为 FR 基因的失活先于邻近肿瘤抑制基因的功能丧失。

在《细胞报告》上发表的一项新研究中，作者开发了一种创新的全器官作图方法，该方法与基因组标记相结合，可以帮助剖析肿瘤前克隆的初始克隆扩增的事件序列。该策略用于鉴定肿瘤抑制因子RB1周围区域的 FR 基因。鉴定出一个 1.7 Mb 的最小片段，其多态性的丧失与肿瘤前克隆的早期克隆扩增相关，并且包括 20 个假定的候选基因。对RB1周围 5 Mb 片段的表达研究能够鉴定出 5 个 FR 基因，这些基因的表达在 >50% 的样本中至少下调两倍： ITM2B 、 LPAR6 、 MLNR 、 CAB39L和ARL11 。超甲基化被确定为这些基因沉默的主要机制。