Section 1 Basic Knowledge

**3**

**Chapter 1**

**Abstract**

**1. History**

**1.1 Introduction**

History and Genetics of

*Leen Abu Safieh and Saad Aldahmash*

and counseling for patients with retinoblastoma.

epigenetics, Knudson, allele, germline, somatic

*Tariq Alzahem, Waleed Alsarhani, Abdullah Albahlal,* 

The history of retinoblastoma (RB) goes back to 1597 when Pieter Pawius of Amsterdam described a tumor that resembled retinoblastoma. "Fungus haematodes" was the first term used to describe retinoblastoma. Later, the American Ophthalmological Society approved the term retinoblastoma in 1926. The retinoblastoma protein is encoded by the RB1 gene located at 13q14. The functioning model of the tumor suppressor genes was first proposed by Alfred Knudson in the 1970s who precisely explained the hereditary mechanism of retinoblastoma. If both alleles of this gene are mutated, the protein is inactivated and this results in the development of retinoblastoma. One mutation can be either germline or somatic and the second one is always somatic. Differentiation between sporadic and germline retinoblastoma variants requires the identification of the RB1 germline status of the patient. This identification is important for assessing the risk of additional tumors in the same eye, the other eye, and the risk of secondary tumors. Thus, genetic testing is an important component of the management of all children diagnosed with retinoblastoma. In this chapter, we will go over the history, genetics,

**Keywords:** history, genetics, two-hit hypothesis, RB1 gene, tumor suppressor,

Different tumors that resembled retinoblastoma were described in the past, the first of which was by Pieter Pawius of Amsterdam in 1597 [1]. The Dutch anatomist described a malignancy involving the left eye, temporal bone, and cranium [1]. Pawius described the tumor as "filled with substance like brain tissue mixed with thick blood and like crushed stone." The crushed stone may have represented retinoblastoma classic calcifications. Then, in 1767, Hayes described another case of a child who had presented with the appearance "cat's eyes in the dark" [2]. This was the first description of leukocoria in the scientific literature. In the last two centuries, retinoblastoma had different names. "Fungus haematodes" was the term used in the early 1800s. This term was used to describe a fungating vascular tumor that affected different parts of the body including the globe. Before the era of ophthalmoscopy, no one thought the tumor originated from the globe except

Retinoblastoma
