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Purpose: H3B-6545, a novel Selective ERα Covalent Antagonist (SERCA), inactivates both and wild-type and mutant ERα by targeting cysteine 530 and enforcing antagonist conformation. H3B-6545 demonstrated preclinical high activity in breast cancer models with constitutively active ESR1 mutations (Furman C, SABCS 2020) and clinical activity in pretreated women with ER+ breast cancer (Hamilton EP, ASCO 2021). Patients and Methods: The primary objective of the phase II is to estimate the objective response rate (ORR), clinical benefit rate (CBR), progression-free survival (PFS), and secondary objectives include safety. Results: 94 pts were treated with 450 mg daily, the recommended phase II dose: 11 in the phase I and 83 in the phase II parts of the trial. Patients and tumor characteristics were presented previously (Hamilton EP, ASCO, 2021). As of March 31, 2021, grade (gr) 2 or higher adverse events (AE) reported in ≥10% were anemia (19%), nausea (17%), fatigue (16%), and diarrhea (12%). Laboratory gr 2 or higher abnormalities reported in ≥10% pts were creatinine clearance decrease (39%), hemoglobin decrease (38%), Lymphocytes decrease (37%), ALT increase (14%), AST increase (13%), bilirubin increase (12%), and creatinine increase (12%). AE of gr 1 sinus bradycardia (asymptomatic) was reported in 35% and gr 2 (symptomatic, no intervention needed) was reported in 5%. Gr 2 and 3 QTcF prolongation were reported in 2 and 3 pts, respectively. There were no treatment-related deaths. Efficacy estimates are presented in Table 1. CI: Confidence interval. N: total number of pts in full analysis set, used in PFS analysis. n: number of response-evaluable pts, used in ORR and CBR analysis. Efficacy estimates were consistent across the various subgroups. Responses were demonstrated in heavily pretreated pts, pts with visceral metastases, pts with constitutionally active ESR1 Y537S mutations, and in pts who received chemotherapy in the metastatic setting. Numerically higher response rate and longer PFS were observed in pts with ESR1 Y537s. Conclusions: H3B-6545 has a manageable safety profile and demonstrated single-agent anti-tumor activity in heavily pretreated ER+, HER2- mBC patients. Clinical activity was consistent across the various subgroups. Tumors harboring the constitutionally active ESR1 Y537S mutation may present higher ERα activity, and consequently enrich for luminal A traits and demonstrate greater lineage dependence on ERα. Table 1.Consistency of H3B-6545 activity across the key subgroupsEfficacyClinical CharacteristicORR % (95% CI)CBR % (95% CI)Median PFS mo (95% CI)Overall population (N=94, n=72)16.7 (8.9, 27.3)40.3 (28.9, 52.5)5.1 (3.2, 6.2)Liver and/or lung metastases (N=76, n=62)17.7 (9.2, 29.5)41.9 (29.5, 55.2)5.4 (1.8, 7.2)≥3 prior regimens (N=49, n=39)20.5 (9.3, 36.5)48.7 (32.4, 65.2)5.4 (3.5, 7.3)Prior chemotherapy (N=47, n=35)17.1 (6.6, 33.6)51.4 (34.0, 68.6)5.5 (3.6, 7.3)PgR+ (N=38, n=32)15.6 (5.3, 32.8)50.0 (31.9, 68.1)5.4 (2.0, 8.8)ESR1 clonal Y537S (N=10, n=10)30.0 (6.7, 65.2)60.0 (26.2, 87.8)7.3 (0.8, 11.2)ESR1 clonal D538G (N=19, n=17)0.0 (0.0, 19.5)35.3 (14.2, 61.7)5.4 (1.7, 7.2) Citation Format: Erika P Hamilton, Judy S Wang, Timothy Pluard, Aki Morikawa, E Claire Dees, Robert H Jones, Barbara Haley, Anne Armstrong, Adam L Cohen, Pamela Munster, Gail S Wright, Fadi Kayali, Lisa Cantagallo, Manav Korpal, Jenny Long, Jianjun Xiao, Benoit Destenaves, Lei Gao, Tarek Sahmoud, Antonio Gualberto, Dejan Juric. H3B-6545, a novel selective estrogen receptor covalent antagonist (SERCA), in estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer - A phase II study [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-17-10.

PURPOSEWe report the results from a Foundation for the National Institutes of Health Biomarkers Consortium project to address the absence of well-validated quality control materials (QCMs) for circulating tumor DNA (ctDNA) testing. This absence is considered a cause of variance and inconsistencies in translating ctDNA results into clinical actions.METHODSIn this phase I study, QCMs with 14 clinically relevant mutations representing single nucleotide variants, insertions or deletions (indels), translocations, and copy number variants were sourced from three commercial manufacturers with variant allele frequencies (VAFs) of 5%, 2.5%, 1%, 0.1%, and 0%. Four laboratories tested samples in quadruplicate using two allele-specific droplet digital polymerase chain reaction and three (amplicon and hybrid capture) next-generation sequencing (NGS) panels.RESULTSThe two droplet digital polymerase chain reaction assays reported VAF values very close to the manufacturers’ claimed concentrations for all QCMs. NGS assays reported most single nucleotide variants and indels, but not translocations, close to the expected VAF values. Notably, two NGS assays reported lower VAF than expected for all translocations in all QCM mixtures, possibly related to technical challenges detecting these variants. The ability to call ERBB2 copy number amplifications varied across assays. All three QCMs provided valuable insight into assay precision. Each assay across all variant types demonstrated dropouts at 0.1%, suggesting that the QCM can serve for testing of an assay’s limit of detection with confidence claims for specific variants.CONCLUSIONThese results support the utility of the QCM in testing ctDNA assay analytical performance. However, unique designs and manufacturing methods for the QCM, and variations in a laboratory’s testing configuration, may require testing of multiple QCMs to find the best reagents for accurate result interpretation.

We conducted a phase I clinical trial of H3B-8800, an oral small molecule that binds Splicing Factor 3B1 (SF3B1), in patients with MDS, CMML, or AML. Among 84 enrolled patients (42 MDS, 4 CMML and 38 AML), 62 were red blood cell (RBC) transfusion dependent at study entry. Dose escalation cohorts examined two once-daily dosing regimens: schedule I (5 days on/9 days off, range of doses studied 1–40 mg, n = 65) and schedule II (21 days on/7 days off, 7–20 mg, n = 19); 27 patients received treatment for ≥180 days. The most common treatment-related, treatment-emergent adverse events included diarrhea, nausea, fatigue, and vomiting. No complete or partial responses meeting IWG criteria were observed; however, RBC transfusion free intervals >56 days were observed in nine patients who were transfusion dependent at study entry (15%). Of 15 MDS patients with missense SF3B1 mutations, five experienced RBC transfusion independence (TI). Elevated pre-treatment expression of aberrant transcripts of Transmembrane Protein 14C (TMEM14C), an SF3B1 splicing target encoding a mitochondrial porphyrin transporter, was observed in MDS patients experiencing RBC TI. In summary, H3B-8800 treatment was associated with mostly low-grade TAEs and induced RBC TI in a biomarker-defined subset of MDS.

e13025 Background: H3B-6545, a highly Selective ERα Covalent Antagonist (SERCA), inactivates both wild-type and mutant ERα by targeting cysteine 530 and enforcing a unique antagonist conformation. At the dose of 450 mg daily, H3B-6545 has a manageable safety profile and demonstrated preliminary single-agent antitumor activity in heavily pretreated ER+, HER2- mBC patients (Hamilton et al, San Antonio Breast Cancer Symposium, 2020). Methods: The study evaluates the safety, pharmacokinetics (PK), and efficacy of H3B-6545 in combination with palbociclib in patients with ER+, HER2- metastatic breast cancer (MBC). The escalation phase enrolls patients with 2 or more prior therapies in the metastatic setting. Up to one prior chemotherapy and up to one prior CDK4/6 inhibitor were allowed. Results: As of January 31, 2021, 10 patients were enrolled; 7 in Cohort 1 (H3B-6545 300 mg QD and palbociclib 100 mg QD) and 3 in Cohort 2 (H3B-6545 300 mg QD and palbociclib 125 mg QD). One patient in Cohort 1 was not evaluable for dose limiting toxicity (DLT) assessment and no DLT was observed in the 6 evaluable patients. One patient discontinued study treatment because of progression and no patients discontinued study treatment due to adverse events (AE). Grade 3 or 4 neutropenia and thrombocytopenia were observed in 4 patients and 1 patient, respectively. One patient had grade 3 hypercalcemia, generalized muscle weakness, hypophosphatemia, fall, and anemia and one patient had grade 3 lipase increase. Four patients had grade 1 bradycardia or sinus bradycardia (asymptomatic) 1 patient had grade 2 sinus bradycardia (symptomatic, no intervention required). Preliminary PK analysis suggested no clinically relevant drug-drug interactions between H3B-6545 and palbociclib, to be confirmed with data from additional cohorts. Recruitment is currently ongoing in Cohort 2. Updated results will be presented. Conclusions: H3B-6545, in combination with palbociclib, was well-tolerated. Clinical trial information: NCT04288089.

4090 Background: Evidence suggests that hyperactivated fibroblast growth factor 4 (FGFR4) signaling pathway leads to enhanced tumor growth. Targeting FGFR4 may have therapeutic benefit in tumors with altered FGF19 signaling. A phase I study (NCT02834780) was undertaken to assess H3B-6527, a highly selective covalent FGFR4 inhibitor, in patients with HCC/ICC. Methods: Adults with advanced HCC/ICC, ECOG PS 0-1, well compensated liver function, who progressed after > one prior therapy, received H3B-6527 po daily (QD) or twice-daily (bid) on a 21-day cycle following a 3+3 design. Doses ranged from 300-2000mg QD or 500-700mg BID. Patients in dose escalation were treated regardless of FGF19 status. Patients in expansion had FGF19+ tumors by mRNA testing. Adverse events (AEs), and pharmacokinetics (PK) were assessed. Response was determined by RECIST 1.1/mRECIST imaging every 6 weeks. Results: Study enrollment is complete at 128 patients. Ninety HCC patients were treated (QD = 48, bid = 42). ICC enrollment was suspended after 38 patients due to limited efficacy. No dose-limiting toxicities were seen and no grade 4-5 treatment related AEs have been observed. Recommended Phase II dose for H3B-6527 is 1000mg QD based upon safety, efficacy, and PK data. Grade 3 TEAEs have occurred in 12.5% of patients on QD dosing. Treatment related TEAEs were seen in 62.5% of patients on the QD schedule, with diarrhea (45.8%), fatigue (12.5%), and nausea (12.5%) most frequent. Drug discontinuation due to AEs for QD dosing was 8.3%. Interim data analysis shows that, for HCC patients with >2 prior lines of therapy treated on QD schedule, overall survival was 10.6m, progression-free survival 4.1m, overall response rate 16.7% (all partial responses), and clinical benefit rate 45.8% (responders + durable stable disease >17 weeks). H3B-6527 Cmax and AUC were lower at 300 mg dose but then similar across 500–2000 mg doses. Following oral administration of 1000 mg fasted, H3B-6527 plasma concentration reached peak at a Tmax of ̃2-3 hours and then decayed exponentially, with terminal half-life of ̃4-5 hours. There was no accumulation following QD dose. Dosing with food did not meaningfully change H3B-6527 plasma exposure. Conclusions: H3B-6527 was well tolerated and demonstrated a favorable toxicity and safety profile and encouraging clinical activity in heavily pretreated HCC patients. Final trial results will be presented at conference. Clinical trial information: NCT02834780.

1018 Background: H3B-6545, a selective, small molecule covalent antagonist of ERα demonstrated preclinical and preliminary clinical activity against ER+ breast cancer (Hamilton EP, SABCS, 2020). This study evaluated the activity and tolerability of H3B-6545 in patients (pts) with metastatic ER+, HER2-, breast cancer refractory to endocrine therapy. Methods: Patients received H3B-6545 once daily at the recommended phase II dose of 450 mg. The primary objective of the phase II is to estimate the objective response rate (ORR), progression-free survival (PFS), clinical benefit rate (CBR) and secondary objectives include safety. Results: 83 pts were treated with 450 mg in the phase II part of the trial. Additionally, 11 pts were treated with 450 mg in the phase I part of the trial and are included in this analysis. Median age was 62 years (range: 38 to 87 years), 81% had liver and/or lung metastases, and the median number of prior therapies for metastatic disease was 3 (range: 1 to 8). Prior CDK4/6 inhibitors, aromatase inhibitors, fulvestrant, and chemotherapy were received by 85%, 80%, 72%, and 50% of the pts, respectively. 58 pts (62%) had detectable ESR1 mutations in liquid biopsies, including 10 (11%) and 19 pts (20%) who had clonal Y537S and clonal D538G mutation, respectively. As of January 29, 2021, grade (gr) 2 or higher adverse events (AE) reported in ≥10% were anemia (19%), fatigue (16%), nausea (17%), and diarrhea (12%). Laboratory gr 2 or higher abnormalities reported in ≥10% pts were creatinine clearance decrease (38%), hemoglobin decrease (37%), bilirubin increase (12%), ALT increase (14%), AST increase (13%), and creatinine increase (11%). AE of gr 1 sinus bradycardia (asymptomatic) was reported in 34% and gr 2 (symptomatic, no intervention needed) was reported in 5%. Gr 2 and 3 QTcF prolongation were reported in 2 and 3 pts, respectively. There were no treatment-related deaths. Efficacy estimates are presented in the table below. Responses were observed in heavily pretreated pts, pts with visceral metastases and in pts who received prior fulvestrant, CDK4/6 inhibitor, and/or chemotherapy in the metastatic setting. Conclusions: H3B-6545 has a manageable safety profile and demonstrated single-agent anti-tumor activity in heavily pretreated ER+, HER2- mBC patients. Clinical activity was observed in pts with ESR1 mutations. Clinical trial information: NCT03250676 .[Table: see text]

Background: Addition of CDK 4/6 inhibitors to endocrine therapy has provided significant improvements in outcomes for patients (pts) with metastatic breast cancer (mBC). However, acquired resistance to front-line therapy remains a challenge, and response to late lines of therapy is poor. H3B-6545 is a selective, orally available, small molecule covalent antagonist of the estrogen receptor (ERα) H3B-6545 binds covalently to a cysteine residue at position 530 of both wild-type and the constitutively active mutant ERα proteins, including Y537S. H3B-6545 demonstrated significant antitumor activity in multiple PDX breast cancer models, including those with mutated ESR1 (the gene encoding ERα).Methods: This is a multicenter phase I/II trial. The primary objective of the phase I is to determine the maximum tolerated dose and recommended phase 2 dose (RP2D) in pretreated pts with ER+, HER2- mBC. Secondary objectives include safety and antitumor activity. The primary objective of the phase II is to estimate the objective response rate (ORR) and secondary objectives include clinical benefit rate (CBR), progression-free survival (PFS) and safety. The trial was designed to exclude a lower limit of ORR of 5% at one-sided level of significance of 0.05 and a power of 90%. Results: Between August 2017 and February 2020, 130 pts were enrolled; 47 in the Phase I part and 83 in the Phase II part of the trial. A total of 105 pts, including 73 patients on 450 mg, were response-evaluable. The phase I evaluated once daily doses from 100 to 600 mg. No dose-limiting toxicities (DLT) were observed at doses up to 450 mg and 2 DLTs were observed in 2 (grade 3 fatigue and grade 3 drug eruption) of 7 pts on the 600 mg cohort. Consequently, the dose of 450 mg was selected as the RP2D. Median age was 62 years (range: 31 to 87 years), 82% had liver and/or lung metastases, and the median number of prior therapies for metastatic disease was 3 (range: 1 to 10), with 41% of the pts receiving ≥ 4 prior therapies in the metastatic setting. Prior CDK4/6 inhibitors, fulvestrant, and chemotherapy were received by 87%, 71%, and 54% of the pts, respectively. 75 pts (58%) had detectable ESR1 mutations. As of May 31, 2020, grade 2 or higher adverse events reported in ≥10% were anemia (20%), fatigue (16%), nausea (14%), diarrhea (11%) and AST increase (11%). Three cases of grade 4 AE were reported (serum bilirubin, urinary tract obstruction, and hyponatremia), all considered related to disease progression. Grade 1 sinus bradycardia (asymptomatic) was reported in 35% and grade 2 (symptomatic, no intervention needed) was reported in 4%. Grade 2 and 3. QTcF prolongation were reported in 2 and 3 patients, respectively. There were no treatment-related deaths. In the response-evaluable group, 13 confirmed partial responses (PR, 12%. 90% confidence limits: 7.5%-19%), including 11 PRs (15%, 90% confidence limits: 8.7%-23.7) on 450 mg dose, were observed, thus achieving the primary objective of the trial. Stable disease (SD) and clinical benefit rates (≥23 weeks) were 45% and 33% respectively at 450 mg and 46% and 34%, respectively on all doses. Responses were observed in heavily pretreated pts, pts with visceral metastases and in pts who received prior fulvestrant, prior CDK4/6 inhibitor, and/or prior chemotherapy, in the metastatic setting. Three PRs (25%) and 4 SDs were observed in 12 pts in whom clonal ESR1 Y537S was the main ERα driver. Median PFS, in all pts and in pts with clonal ESR1 Y537S was 3.7 months and 7.3 months, respectively. Conclusions: H3B-6545 has a manageable safety profile and demonstrated single-agent anti-tumor activity in heavily pretreated ER+, HER2- mBC patients including those with a constitutively active clonal ESR1 Y537S mutation. Citation Format: Erika P Hamilton, Judy S Wang, Timothy Pluard, Stephen Johnston, Aki Aki Morikawa, Claire E Dees, Robert H Jones, Barbara Haley, Anne Armstrong, Adam L Cohen, Pamela Munster, Gail Wright, Fadi Kayali, Manav Korpal, Lihua Yu, Lisa Cantagallo, Benoit Destenaves, Zhaojie Zhang, Lei Gao, Marc J Pipas, Tarek Sahmouud, Antonio Gualberto, Dejan Juric. Phase I/II trial of H3B-6545, a novel selective estrogen receptor covalent antagonist (SERCA), in estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD8-06.

textabstractBackground:The current biomarkers alpha-fetoprotein and human chorionic gonadotropin have limited sensitivity and specificity for diagnosing malignant germ-cell tumours (GCTs). MicroRNAs (miRNAs) from the miR-371-373 and miR-302/367 clusters are overexpressed in all malignant GCTs, and some of these miRNAs show elevated serum levels at diagnosis. Here, we developed a robust technical pipeline to quantify these miRNAs in the serum and cerebrospinal fluid (CSF). The pipeline was used in samples from a cohort of exclusively paediatric patients with gonadal and extragonadal malignant GCTs, compared with appropriate tumour and non-tumour control groups.Methods:We developed a method for miRNA quantification that enabled sample adequacy assessment and reliable data normalisation. We performed qRT-PCR profiling for miR-371-373 and miR-302/367 cluster miRNAs in a total of 45 serum and CSF samples, obtained from 25 paediatric patients.Results:The exogenous non-human spike-in cel-miR-39-3p and the endogenous housekeeper miR-30b-5p were optimal for obtaining robust serum and CSF qRT-PCR quantification. A four-serum miRNA panel (miR-371a-3p, miR-372-3p, miR-373-3p and miR-367-3p): (i) showed high sensitivity/specificity for diagnosing paediatric extracranial malignant GCT; (ii) allowed early detection of relapse of a testicular mixed malignant GCT; and (iii) distinguished intracranial malignant GCT from intracranial non-GCT tumours at diagnosis, using CSF and serum samples.Conclusions:The pipeline we have developed is robust, scalable and transferable. It potentially promises to improve clinical management of paediatric (and adult) malignant GCTs.

Our molecular understanding of growth hormone-induced signal transduction has improved significantly over the past decades. At the same time, human population genetics and the analysis of genetically engineered animals have led to the discovery of genes that control specific aspects of the overall growth process. Although, currently, growth disorders are still diagnosed and treated on empirical bases, it might soon be possible to stratify patients predominantly by genetic defect, with treatment based on our molecular understanding of the role of the affected gene in the disease.

Meta-analysis has shown a modest improvement in first-year growth response to recombinant human GH (r-hGH) for carriers of the exon 3-deleted GH receptor (GHRd3) polymorphism but with significant interstudy variability. The associations between GHRd3 and growth response to r-hGH over 3 years in relation to severity of GH deficiency (GHD) were investigated in patients from 14 countries. Treatment-naïve pre-pubertal children with GHD were enrolled from the PREDICT studies (NCT00256126 and NCT00699855), categorized by peak GH level (peak GH) during provocation test: ≤4 μg/l (severe GHD; n=45) and >4 to n=49) and genotyped for the GHRd3 polymorphism (full length (fl/fl, fl/d3, d3/d3). Gene expression (GE) profiles were characterized at baseline. Changes in growth (height (cm) and SDS) over 3 years were measured. There was a dichotomous influence of GHRd3 polymorphism on response to r-hGH, dependent on peak GH level. GH peak level (higher vs lower) and GHRd3 (fl/fl vs d3 carriers) combined status was associated with height change over 3 years (P

In the years to come, pharmacogenomics will make an impact on the development of new drugs. Numerous publications have shown that gene polymorphism can influence drug toxicity and/or efficacy. In order to improve current applications of pharmacogenomics, some technical limitations regarding marker generation, genotyping and biostatistical analysis are being overcome.

Objective: Individual sensitivity to recombinant human GH (r-hGH) is variable. Identification of genetic factors contributing to this variability has potential use for individualization of treatment. The objective of this study was to identify genetic markers and gene expression profiles associated with growth response on r-hGH therapy in treatment-naïve, prepubertal children with GH deficiency (GHD) or Turner syndrome (TS). Design: A prospective, multicenter, international, open-label pharmacogenomic study. Methods: The associations of genotypes in 103 growth- and metabolism-related genes and baseline gene expression profiles with growth response to r-hGH (cm/year) over the first year were evaluated. Genotype associations were assessed with growth response as a continuous variable and as a categorical variable divided into quartiles. Results: Eleven genes in GHD and ten in TS, with two overlapping between conditions, were significantly associated with growth response either as a continuous variable (seven in GHD, two in TS) or as a categorical variable (four more in GHD, eight more in TS). For example, in GHD, GRB10 was associated with high response (≥Q3; P=0.0012), while SOS2 was associated with low response (≤Q1; P=0.006), while in TS, LHX4 was associated with high response (P=0.0003) and PTPN1 with low response (P=0.0037). Differences in expression were identified for one of the growth response-associated genes in GHD (AKT1) and for two in TS (KRAS and MYOD1). Conclusions: Carriage of specific growth-related genetic markers is associated with growth response in GHD and TS. These findings indicate that pharmacogenomics could have a role in individualized management of childhood growth disorders. Fil: Clayton, P.. Royal Manchester Children’s Hospital. Manchester Academic Health Sciences Centre; Reino Unido Fil: Chatelain, P.. Université Claude Bernard. Hopital Mère-Enfant. Département Pediatrie; Francia Fil: Tato, L.. Università degli Studi di Verona. Clinica Pediatrica; Italia Fil: Yoo, H. W.. University of Ulsan. College of Medicine. Asan Medical Center. Department of Pediatrics; Corea del Sur Fil: Ambler, G. R.. University of Sydney. The Children’s Hospital at Westmead; Australia Fil: Belgorosky, Alicia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Quinteiro, S.. Hospital Materno Infantil. Servicio de Pediatría Endocrino; España Fil: Deal, C.. University of Montreal. Department of Pediatrics; Canadá Fil: Stevens, A.. Royal Manchester Children’s Hospital. Manchester Academic Health Sciences Centre; Reino Unido Fil: Raelson, J.. Genizon BioSciences; Canadá Fil: Croteau, P.. Genizon BioSciences; Canadá Fil: Destenaves, B.. Merck Serono S.A.; Suiza Fil: Olivier, C.. Merck Serono S.A; Suiza

Background A co-ordinated tissue-independent gene expression profile associated with growth is present in rodent models and this is hypothesised to extend to all mammals. Growth in humans has similarities to other mammals but the return to active long bone growth in the pubertal growth spurt is a distinctly human growth event. The aim of this study was to describe gene expression and biological pathways associated with stages of growth in children and to assess tissue-independent expression patterns in relation to human growth. Results We conducted gene expression analysis on a library of datasets from normal children with age annotation, collated from the NCBI Gene Expression Omnibus (GEO) and EBI Arrayexpress databases. A primary data set was generated using cells of lymphoid origin from normal children; the expression of 688 genes (ANOVA false discovery rate modified p-value, q