# Case Report: An uncommon germline variant of familial GISTs: broadening the landscape of inherited GIST syndromes

## TL;DR

This case report describes two family members with inherited gastrointestinal stromal tumors (GISTs) caused by a rare germline KIT gene variant, expanding the known genetic causes of familial GIST.

## Contribution

The study identifies a novel germline KIT variant in Exon 11 (c.1735_1737del) associated with familial GIST and demonstrates successful treatment with Imatinib.

## Key findings

- Two family members with multifocal GISTs were found to have a germline KIT gene variant (c.1735_1737del).
- Both patients responded well to treatment with Imatinib.
- The variant expands the genetic landscape of inherited GIST syndromes.

## Abstract

Familial Gastrointestinal Stromal tumors (GIST) are rare neoplasms but GIST tumors are some of the most common soft tissue sarcoma subtypes. The incidence is between 10 to 15 cases per million worldwide and approximately 500 cases in the USA [1]. GIST is often diagnosed based on clinical presentation, the tumor’s anatomic location and immunohistochemistry (IHC) pattern [1]. Patients with familial GIST develop GIST tumors that are numerous, smaller in size, and occur in the background of intestinal cells of Cajal hyperplasia [2]. The first family with features of inherited GIST was reported in the 1990s which was the first time Exon 11 KIT variant was reported [3]. We present two cases of family members affected with multifocal GIST tumors who underwent germline genetic analysis and were found to have germline pathogenic variants in Exon 11 of the KIT gene [c.1735_1737del (p.Asp579del)]. Both patients were treated with Imatinib with good response.